Publications

 

  • [DOI] C. Ching, B. Yang, C. Onwubueke, D. Lazinski, A. Camilli, and V. G. Godoy, “Lon protease has multifaceted biological functions in Acinetobacter baumannii.,” Journal of bacteriology, p. JB.00536–18, 2018.
    [Bibtex]
    @article{Ching2018,
    abstract = {Acinetobacter baumannii is a Gram-negative opportunistic pathogen known to survive harsh environmental conditions and is a leading cause of hospital-acquired infections. Specifically, multicellular communities, known as biofilms, of A. baumannii can withstand desiccation and survive on hospital surfaces and equipment. Biofilms are bacteria embedded in a self-produced extracellular matrix composed of proteins, sugars and/or DNA. Bacteria in a biofilm are protected from environmental stress, including antibiotics, providing them with selective advantage for survival. Though some gene products are known to play roles in this developmental process in A. baumannii, mechanisms and signaling remain mostly unknown. Here, we find that Lon protease in A. baumannii impacts biofilm development and has other important physiological roles, including motility and cell envelope. Lon proteases are found in all domains of life participating in regulatory processes and maintaining cellular homeostasis. These data reveal the importance of Lon protease in influencing key A. baumannii processes to survive stress and maintain viability.IMPORTANCEAcinetobacter baumannii is an opportunistic pathogen and leading cause of hospital-acquired infections. A. baumannii is difficult to eradicate and manage, as this bacterium is known to robustly survive desiccation and quickly gain antibiotic resistances. We sought to investigate biofilm formation in A. baumannii since much remains unknown about it in this bacterium. Biofilms, which are multicellular communities of bacteria, are surface-attached and difficult to eliminate from hospital equipment and implanted devices. Our research identifies a multi-faceted physiological role of the conserved bacterial protease Lon in A. baumannii These roles include biofilm formation, motility and viability. This work broadly impacts and expands the biology of A. baumannii, which will in turn permit us to find effective ways to eliminate it.},
    author = {Ching, Carly and Yang, Brendan and Onwubueke, Chineme and Lazinski, David and Camilli, Andrew and Godoy, Veronica G},
    doi = {10.1128/JB.00536-18},
    file = {:Users/merlin/Library/Application Support/Mendeley Desktop/Downloaded/Ching et al. - 2018 - Lon protease has multifaceted biological functions in Acinetobacter baumannii.pdf:pdf},
    issn = {1098-5530},
    journal = {Journal of bacteriology},
    month = {oct},
    pages = {JB.00536--18},
    pmid = {30348832},
    publisher = {American Society for Microbiology Journals},
    title = {{Lon protease has multifaceted biological functions in Acinetobacter baumannii.}},
    url = {http://www.ncbi.nlm.nih.gov/pubmed/30348832},
    year = {2018}
    }
  • [DOI] M. G. Prentiss, V. Godoy, C. Danilowicz, C. Prevost, T. Tashjian, and C. Li, “The sequences near Chi sites allow the RecBCD pathway to avoid genomic rearrangements,” Biorxiv, p. 351395, 2018.
    [Bibtex]
    @article{Prentiss2018,
    abstract = {Bacterial recombinational repair is initiated by RecBCD, which creates a 3′ single-stranded DNA (ssDNA) tail on each side of a double strand break (DSB). Each tail terminates in a Chi site sequence that is usually distant from the break. Once an ssDNA-RecA filament forms on a tail, the tail searches for homologous double-stranded DNA (dsDNA) to use as template for DSB repair. Here we show that the nucleoprotein filaments rarely trigger sufficient synthesis to form an irreversible repair unless a long strand exchange product forms at the 3′ end of the filament. Our experimental data and modeling suggest that terminating both filaments with Chi sites allows recombinational repair to strongly suppress fatal genomic rearrangements resulting from mistakenly joining different copies of a repeated sequence after a DSB has occurred within a repeat. Taken together our evidence highlights cellular safe fail mechanisms that bacteria use to avoid potentially lethal situations.},
    author = {Prentiss, Mara Goff and Godoy, Veronica and Danilowicz, Claudia and Prevost, Chantal and Tashjian, Tommy and Li, Chastity},
    doi = {10.1101/351395},
    file = {:Users/merlin/Library/Application Support/Mendeley Desktop/Downloaded/Prentiss et al. - 2018 - The sequences near Chi sites allow the RecBCD pathway to avoid genomic rearrangements.pdf:pdf},
    journal = {bioRxiv},
    month = {jun},
    pages = {351395},
    publisher = {Cold Spring Harbor Laboratory},
    title = {{The sequences near Chi sites allow the RecBCD pathway to avoid genomic rearrangements}},
    url = {https://www.biorxiv.org/content/early/2018/06/20/351395},
    year = {2018}
    }
  • [DOI] B. Nguyen, T. Tashjian, and V. Godoy, “Investigating the Role of DNA Polymerase IV in the Resolution of R-loops,” The faseb journal, vol. 32, iss. 1{_}supplement, p. 646.6–646.6, 2018.
    [Bibtex]
    @article{doi:10.1096/fasebj.2018.32.1\_supplement.646.6,
    abstract = { As the replication fork progresses through the DNA template, it may encounter a number of obstacles, one of which is the RNA transcription machinery. This encounter occurs because both processes utilize the same template and because the rate of replication ({\~{}}1000 nt/s) is much faster than the rate of transcription (40–80 nt/s). The encounter of the two machineries, in either a co-directional or a head-on orientation, results in replication-transcription collisions (RTCs). Failure to resolve these collisions leads to replication fork stalling and eventually cell death. One of the events required to resolve RTCs is the removal of RNA: DNA hybrids, known as R-loops. In E. coli, RNase H1, coded by rnhA, is a member of a family of highly conserved endonucleases mediating resolution of R-loops by cleaving the RNA strand on RNA: DNA hybrids. If not resolved, R-loops cause genomic instability in the form of double-stranded breaks through the collapse of the replication fork and accumulation of DNA lesions. In E. coli, both replication stalling and accumulation of DNA lesions leads to induction of the SOS response. Among the first genes to be upregulated is dinB, encoding DNA polymerase IV (DinB), becoming the most abundant DNA polymerase in the cell ({\~{}}2500 nM). DinB main role is to synthesize DNA over template lesions. There is evidence to support the notion that DinB is involved in recombination, a mechanism that is used to repair double-stranded breaks. In stressful conditions, DinB, due to its abundance, outcompetes other polymerases for the recombination intermediate and synthesizes DNA from it. Because of its abundance during SOS induction and its role in recombination, DinB may also be involved in the resolution of R-loops. Here, we investigate the possible role of DinB in R-loop resolution in a rnhA-deletion strain. Loss of rnhA results in slow growth that is rescued by expression of DinB from a low copy plasmid. This data suggest DinB is multicopy suppressor of the rnhA deletion and that DinB plays a role in the resolution of R-loops. Support or Funding Information National Institute of General Medical Sciences (RO1GM088230 to VG) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal. },
    author = {Nguyen, Brian and Tashjian, Tommy and Godoy, Veronica},
    doi = {10.1096/fasebj.2018.32.1_supplement.646.6},
    journal = {The FASEB Journal},
    number = {1{\_}supplement},
    pages = {646.6--646.6},
    title = {{Investigating the Role of DNA Polymerase IV in the Resolution of R-loops}},
    url = {https://www.fasebj.org/doi/abs/10.1096/fasebj.2018.32.1{\_}supplement.646.6},
    volume = {32},
    year = {2018}
    }
  • [DOI] K. Gozzi, C. Ching, S. Paruthiyil, Y. Zhao, V. Godoy-Carter, and Y. Chai, “Bacillus subtilis utilizes the DNA damage response to manage multicellular development,” Npj biofilms and microbiomes, 2017.
    [Bibtex]
    @article{Gozzi2017,
    abstract = {Bacteria switch between free-living and a multicellular state, known as biofilms, in response to cellular and environmental cues. It is important to understand how these cues influence biofilm development as biofilms are not only ubiquitous in nature but are also causative agents of infectious diseases. It is often believed that any stress triggers biofilm formation as a means of bacterial protection. In this study, we propose a new mechanism for how cellular and environmental DNA damage may influence biofilm formation. We demonstrate that Bacillus subtilis prevents biofilm formation and cell differentiation when stressed by oxidative DNA damage. We show that during B. subtilis biofilm development, a subpopulation of cells accumulates reactive oxygen species, which triggers the DNA damage response. Surprisingly, DNA damage response induction shuts off matrix genes whose products permit individual cells to stick together within a biofilm. We further revealed that DDRON cells and matrix producers are mutually exclusive and spatially separated within the biofilm, and that a developmental checkpoint protein, Sda, mediates the exclusiveness. We believe this represents an alternative survival strategy, ultimately allowing cells to escape the multicellular community when in danger.},
    author = {Gozzi, Kevin and Ching, Carly and Paruthiyil, Srinand and Zhao, Yinjuan and Godoy-Carter, Veronica and Chai, Yunrong},
    doi = {10.1038/s41522-017-0016-3},
    isbn = {2055-5008 (Print) 2055-5008},
    issn = {20555008},
    journal = {npj Biofilms and Microbiomes},
    pmid = {28649409},
    title = {{Bacillus subtilis utilizes the DNA damage response to manage multicellular development}},
    year = {2017}
    }
  • [DOI] C. Ching, K. Gozzi, B. Heinemann, Y. Chai, and V. G. Godoy, “RNA-mediated cis regulation in Acinetobacter baumannii modulates stress-induced phenotypic variation,” Journal of bacteriology, 2017.
    [Bibtex]
    @article{Ching2017,
    abstract = {In the nosocomial opportunistic pathogen Acinetobacter baumannii, RecA-dependent mutagenesis, which causes antibiotic resistance acquisition, is linked to the DNA damage response (DDR). Notably, unlike the Escherichia coli paradigm, recA and DDR gene expression in A. baumannii is bimodal. Namely, there is phenotypic variation upon DNA damage, which may provide a bet-hedging strategy for survival. Thus, understanding recA gene regulation is key to elucidate the yet unknown DDR regulation in A. baumannii Here, we identify a structured 5' untranslated region (UTR) in the recA transcript which serves as a cis-regulatory element. We show that a predicted stem-loop structure in this 5' UTR affects mRNA half-life and underlies bimodal gene expression and thus phenotypic variation in response to ciprofloxacin treatment. We furthermore show that the stem-loop structure of the recA 5' UTR influences intracellular RecA protein levels and, in vivo, impairing the formation of the stem-loop structure of the recA 5' UTR lowers cell survival of UV treatment and decreases rifampin resistance acquisition from DNA damage-induced mutagenesis. We hypothesize that the 5' UTR allows for stable recA transcripts during stress, including antibiotic treatment, enabling cells to maintain suitable RecA levels for survival. This innovative strategy to regulate the DDR in A. baumannii may contribute to its success as a pathogen.IMPORTANCEAcinetobacter baumannii is an opportunistic pathogen quickly gaining antibiotic resistances. Mutagenesis and antibiotic resistance acquisition are linked to the DNA damage response (DDR). However, how the DDR is regulated in A. baumannii remains unknown, since unlike most bacteria, A. baumannii does not follow the regulation of the Escherichia coli paradigm. In this study, we have started to uncover the mechanisms regulating the novel A. baumannii DDR. We have found that a cis-acting 5' UTR regulates recA transcript stability, RecA protein levels, and DNA damage-induced phenotypic variation. Though 5' UTRs are known to provide stability to transcripts in bacteria, this is the first example in which it regulates a bimodal DDR response through recA transcript stabilization, potentially enabling cells to have enough RecA for survival and genetic variability.},
    author = {Ching, Carly and Gozzi, Kevin and Heinemann, Bj{\"{o}}rn and Chai, Yunrong and Godoy, Veronica G.},
    doi = {10.1128/JB.00799-16},
    issn = {10985530},
    journal = {Journal of Bacteriology},
    keywords = {Acinetobacter,DNA damage,Gene expression,Microbial genetics,Molecular biology,RecA},
    pmid = {28320880},
    title = {{RNA-mediated cis regulation in Acinetobacter baumannii modulates stress-induced phenotypic variation}},
    year = {2017}
    }
  • [DOI] K. Gozzi, C. Ching, S. Paruthiyil, Y. Zhao, V. Godoy-Carter, and Y. Chai, “Bacillus subtilis utilizes the DNA damage response to manage multicellular development,” Npj biofilms and microbiomes, vol. 3, iss. 1, p. 8, 2017.
    [Bibtex]
    @article{Gozzi2017a,
    abstract = {Bacteria switch between free-living and a multicellular state, known as biofilms, in response to cellular and environmental cues. It is important to understand how these cues influence biofilm development as biofilms are not only ubiquitous in nature but are also causative agents of infectious diseases. It is often believed that any stress triggers biofilm formation as a means of bacterial protection. In this study, we propose a new mechanism for how cellular and environmental DNA damage may influence biofilm formation. We demonstrate that Bacillus subtilis prevents biofilm formation and cell differentiation when stressed by oxidative DNA damage. We show that during B. subtilis biofilm development, a subpopulation of cells accumulates reactive oxygen species, which triggers the DNA damage response. Surprisingly, DNA damage response induction shuts off matrix genes whose products permit individual cells to stick together within a biofilm. We further revealed that DDRON cells and matrix producers are mutually exclusive and spatially separated within the biofilm, and that a developmental checkpoint protein, Sda, mediates the exclusiveness. We believe this represents an alternative survival strategy, ultimately allowing cells to escape the multicellular community when in danger.},
    author = {Gozzi, Kevin and Ching, Carly and Paruthiyil, Srinand and Zhao, Yinjuan and Godoy-Carter, Veronica and Chai, Yunrong},
    doi = {10.1038/s41522-017-0016-3},
    file = {:Users/merlin/Library/Application Support/Mendeley Desktop/Downloaded/Gozzi et al. - 2017 - Bacillus subtilis utilizes the DNA damage response to manage multicellular development.pdf:pdf},
    issn = {2055-5008},
    journal = {npj Biofilms and Microbiomes},
    keywords = {Bacteriology,Biofilms,Microbial genetics},
    month = {dec},
    number = {1},
    pages = {8},
    publisher = {Nature Publishing Group},
    title = {{Bacillus subtilis utilizes the DNA damage response to manage multicellular development}},
    url = {http://www.nature.com/articles/s41522-017-0016-3},
    volume = {3},
    year = {2017}
    }
  • [DOI] T. F. Tashjian, I. Lin, V. Belt, T. M. Cafarelli, and V. G. Godoy, “RNA Primer Extension Hinders DNA Synthesis by Escherichia coli Mutagenic DNA Polymerase IV,” Frontiers in microbiology, vol. 08, p. 288, 2017.
    [Bibtex]
    @article{Tashjian2017,
    abstract = {In Escherichia coli the highly conserved DNA damage regulated dinB gene encodes DNA Polymerase IV, an error prone specialized DNA polymerase with a central role in stress-induced mutagenesis. Since DinB is the DNA polymerase with the highest intracellular concentrations upon induction of the SOS response, further regulation must exist to maintain genomic stability. Remarkably, we find that DinB DNA synthesis is inherently poor when using an RNA primer compared to a DNA primer, while high fidelity DNA polymerases are known to have no primer preference. Moreover, we show that the poor DNA synthesis from an RNA primer is conserved in DNA polymerase Kappa, the human DinB homologue. The activity of DinB is modulated by interactions with several other proteins, one of which is the equally evolutionarily conserved recombinase RecA. This interaction is known to positively affect DinB's fidelity on damaged templates. We find that upon interaction with RecA, DinB shows a significant reduction in DNA synthesis when using an RNA primer. Furthermore, with DinB or DinB:RecA a robust pause, sequence and lesion independent, occurs only when RNA is used as a primer. The robust pause is likely to result in abortive DNA synthesis when RNA is the primer. These data suggest a novel mechanism to prevent DinB synthesis when it is not needed despite its high intracellular concentrations protecting thus genome stability.},
    author = {Tashjian, Tommy F. and Lin, Ida and Belt, Verena and Cafarelli, Tiziana M. and Godoy, Veronica G.},
    doi = {10.3389/fmicb.2017.00288},
    file = {:Users/merlin/Library/Application Support/Mendeley Desktop/Downloaded/Tashjian et al. - 2017 - RNA Primer Extension Hinders DNA Synthesis by Escherichia coli Mutagenic DNA Polymerase IV.pdf:pdf},
    issn = {1664-302X},
    journal = {Frontiers in Microbiology},
    keywords = {DNA Replication,DNA polymerase IV,dinB,protein-protein interaction,recA},
    month = {mar},
    pages = {288},
    publisher = {Frontiers},
    title = {{RNA Primer Extension Hinders DNA Synthesis by Escherichia coli Mutagenic DNA Polymerase IV}},
    url = {http://journal.frontiersin.org/article/10.3389/fmicb.2017.00288/full},
    volume = {08},
    year = {2017}
    }
  • [DOI] C. Ching, K. Gozzi, B. Heinemann, and V. G. Godoy, “Investigating the regulation of recA in the emerging pathogen Acinetobacter baumannii,” The faseb journal, vol. 31, iss. 1{_}supplement, p. 591.2–591.2, 2017.
    [Bibtex]
    @article{doi:10.1096/fasebj.31.1\_supplement.591.2,
    abstract = { Acinetobacter baumannii (Ab) is an emerging multidrug-resistant, opportunistic pathogen. Ab survives desiccation, remaining on hospital surfaces affecting immunocompromised individuals. Ab antibiotic resistance acquisition has been linked to its DNA damage response (DDR). DDR genes, including error-prone DNA polymerases, are involved in DNA damage and desiccation induced mutagenesis. In Escherichia coli, RecA, the cells' main recombinase, binds single stranded DNA, the signal of DNA damage, forming the nucleoprotein filament (RecA*), which is endowed with co-protease activity. RecA* promotes cleavage and inactivation of LexA, the global DDR repressor, resulting in expression of DDR genes. In Ab, this well-known circuitry does not exist in part because Ab lacks a functional LexA. We have shown that conserved DDR genes in Ab form two phenotypic subpopulations in response to DNA damage: one with low and another with high expression. The DDR in Ab is dependent on RecA. Thus, we are focused on understanding the mechanism underlying recA regulation to begin to understand the regulatory network that underlies this bimodality. We have found that the recA gene contains a cis-acting element in its 5′ untranslated region (UTR). In-vitro transcription demonstrated that this 5′UTR contains secondary structure. A plasmid-borne reporter was constructed that contains the cis-regulatory element driving a fluorescent reporter. Mutants of the cis-regulatory element that deletes putative regulatory sequences or predicted in silico secondary structure were constructed using site-directed mutagenesis. Using fluorescent microscopy of the reporter strains, we have shown that the cis-acting regulatory element and its structure are important for bimodal expression of recA, while the promoter contains elements for DNA Damage sensing. Furthermore, we found that the recA 5′UTR modulates transcript levels and subsequently RecA in the cell. Disrupting the structure of the 5′UTR results in a significant decrease of UV survival and antibiotic resistance acquisition. This provides evidence that in Ab, two levels of regulation mediate recA. Remarkably, the Ab promoter and UTR sequence is capable of responding not only in Ab but also in other bacterial species as observed through similar fluorescent reporters induced with DNA damaging agents. Bimodal DDR gene expression may provide a strategy for survival and plasticity in an ever-changing environment. These findings may also provide insight into the evolution of other highly antibiotic resistant bacteria lacking conserved DDR gene networks Support or Funding Information NIH Grant (GM088230) to VG },
    author = {Ching, Carly and Gozzi, Kevin and Heinemann, Bjorn and Godoy, Veronica G},
    doi = {10.1096/fasebj.31.1_supplement.591.2},
    journal = {The FASEB Journal},
    number = {1{\_}supplement},
    pages = {591.2--591.2},
    title = {{Investigating the regulation of recA in the emerging pathogen Acinetobacter baumannii}},
    url = {https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1{\_}supplement.591.2},
    volume = {31},
    year = {2017}
    }
  • [DOI] T. Tashjian, J. A. Halliday, C. Herman, and V. Godoy, “Escherichia coli DinB and Replication-Transcription Collisions,” The faseb journal, vol. 31, iss. 1{_}supplement, p. 591.3–591.3, 2017.
    [Bibtex]
    @article{doi:10.1096/fasebj.31.1\_supplement.591.3,
    abstract = { DinB is an error prone DNA polymerase (DNAP) regulated by Escherichia coli's DNA damage response. This enzyme is well known for its translesion synthesis activity, i.e. the ability to bypass potentially lethal lesions on template DNA. Curiously, cells in which DinB is expressed from an inducible promoter in a high copy number plasmid die upon induction of DinB expression. This loss of survival is rescued by a single amino acid substitution (DinB(V7G)), which does not affect DNA synthesis activity in vitro or translesion synthesis activity in vivo. Therefore, DinB(V7G) separates DinB's known function as a translesion synthesis DNAP and an additional unknown role that causes cell death at high intracellular concentrations. We have evidence that suggests DinB plays a role in the resolution of replication-transcription collisions (RTCs). RTCs occur because DNAP III replicates rapidly ({\~{}}1000 nt/s) while RNA polymerase (RNAP) transcribes relatively slowly (40–80 nt/s), and these two processes use the same template DNA at the same time. RTCs are most prevalent in genes encoded on the lagging strand, where DNAP and RNAP collide head on, and on highly expressed genes, regardless of orientation, due to longer RNAP occupancy of the template. Previous studies have identified the transcription factors NusA and DksA as key players in RTC resolution. NusA and DinB interact in E. coli. The nusAts11 allele is thought to cause a lethal frequency of RTCs at 42°C due to failure of RNAP to disengage from the template. The amino acid substitution in nusAts11 occurs at the DinB-NusA binding interface. DinB is known to suppress the nusAts11 phenotype when expressed from a low copy number plasmid under its own promoter. Notably, we find that the DinB(V7G) variant fails to suppress the lethality of the nusAts11 strain at 42°C, though the interacting surface is unlikely changed as the V7 residue is located in the DinB active site. This finding suggests that DinB has an activity related to RTCs that is not performed by the DinB(V7G) variant. Previous studies have shown that DksA prevents RNAP pausing, and thus RTCs, especially during amino acid starvation. Therefore, $\Delta$dksA cells have a notably slower growth during amino acid starvation due to the stalling of RNAP and thus RTCs. We find that this phenotype is exacerbated by DinB expression from its own promoter in a low-copy number plasmid. In the presence of the rpoB2 allele, which encodes an RNAP variant that pauses less frequently and rescues dksA growth reduction in minimal medium, we find that dinB expressed from the low copy number no longer worsens growth rate reduction, suggesting that the DinB effect on growth rate is dependent on RNAP pausing. Interestingly, we found that the DinB(V7G) variant, which suppresses the dinB overproduction phenotype, also rescues the $\Delta$dksA/pDinB+ severe growth reduction phenotype. These data suggest that DinB plays a role in the RTCs. It is likely that the dinB overproduction phenotype is the result of an exacerbation of the RTCs as we uncovered at lower dinB concentrations in the $\Delta$dksA strain. We hypothesize that DinB switches between DNA translesion synthesis and some yet undiscovered activity to help resolving RTCs and that in DinB(V7G) this equilibrium is altered. Support or Funding Information National Institute of General Medical Sciences [RO1GM088230 to V.G.G.] },
    author = {Tashjian, Tommy and Halliday, Jennifer A and Herman, Christophe and Godoy, Veronica},
    doi = {10.1096/fasebj.31.1_supplement.591.3},
    journal = {The FASEB Journal},
    number = {1{\_}supplement},
    pages = {591.3--591.3},
    title = {{Escherichia coli DinB and Replication-Transcription Collisions}},
    url = {https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1{\_}supplement.591.3},
    volume = {31},
    year = {2017}
    }
  • [DOI] T. Tashjian, I. Lin, T. Cafarelli, and V. Godoy, “Investigating the Importance of DinB-RecA Interactions to the Regulation of DinB’s Activity and the Fidelity of the DNA Damage Response,” The faseb journal, vol. 29, iss. 1{_}supplement, p. 561.3, 2015.
    [Bibtex]
    @article{doi:10.1096/fasebj.29.1\_supplement.561.3,
    abstract = { The error prone DNA Polymerase IV, DinB, specializes in synthesizing DNA from a lesion-containing DNA template, an activity that allows cell survival during DNA-damaging conditions at a mutagenic cost. We have shown that there is direct physical interaction between DinB and Escherichia coli's main recombinase, RecA. We also have in vitro evidence suggesting that DinB•RecA interaction is conserved across many bacterial species, including human pathogens. Circular dichroism spectroscopy experiments show that the DinB•RecA complex undergoes a drastic conformational change compared to the single proteins alone. This is supported by the fact that DinB(C66A), a derivative with tight binding to RecA, and RecA copurify by size exclusion chromatography at a size that is much smaller than the size of the individual proteins, suggesting that compaction and tertiary structure changes are likely involved upon complex formation. Alteration of the physical interaction between DinB and RecA leads to changes in the mutagenic outcome in E. coli cells that are exposed to DNA damaging agents. Our current model is that the DinB•RecA complex not only alters the activity of DinB, but results in the sequestration of RecA from the lowest fidelity polymerase, DNA Polymerase V. The DinB•RecA complex, therefore, is central in controlling the fidelity of the DNA damage response. Source of Funding: R01 and its supplement from the National Institute of Health (NIH) Institute of General Medicine to V. Godoy },
    author = {Tashjian, Tommy and Lin, Ida and Cafarelli, Tiziana and Godoy, Veronica},
    doi = {10.1096/fasebj.29.1_supplement.561.3},
    journal = {The FASEB Journal},
    number = {1{\_}supplement},
    pages = {561.3},
    title = {{Investigating the Importance of DinB-RecA Interactions to the Regulation of DinB's Activity and the Fidelity of the DNA Damage Response}},
    url = {https://www.fasebj.org/doi/abs/10.1096/fasebj.29.1{\_}supplement.561.3},
    volume = {29},
    year = {2015}
    }
  • [DOI] C. Ching and V. Godoy, “Insights into the mechanism regulating the DNA Damage Response in Acinetobacter baumannii,” The faseb journal, vol. 29, iss. 1{_}supplement, p. 879.15, 2015.
    [Bibtex]
    @article{doi:10.1096/fasebj.29.1\_supplement.879.15,
    abstract = { Acinetobacter baumannii (Ab) is an emerging multidrug-resistant, opportunistic pathogen. Ab antibiotic resistance acquisition has been linked to its DNA damage response (DDR). DDR genes, including error-prone DNA polymerases IV (DinB) and V (UmuDC), are involved in DNA damage and desiccation induced mutagenesis. In Escherichia coli, RecA, the cells main recombinase, binds single stranded DNA, the signal of DNA damage, forming the nucleoprotein filament which serves as a co-protease. It promotes cleavage and inactivation of LexA, the global DDR repressor, resulting in expression of DDR genes. In Ab, this well-known circuitry does not exist mainly because Ab lacks LexA. We have shown that classical DDR genes in Ab form two phenotypic subpopulations in response to DNA damage: one with low and another with high expression. Our goal is to determine key aspects of Ab's DDR circuitry and its consequences on survival and antibiotic resistance acquisition. We have focused our attention on understanding the mechanism of recA regulation. We have found that the recA promoter contains non-conserved novel regulatory elements. We have evidence that different regulatory motifs are important for expression of recA and moreover that deregulation of recA leads to deregulation of umuDC (which has its own unique promoter sequence).This data suggest that expression of recA has consequences on the expression of error prone DNA polymerase genes forming a regulatory loop, which is typical of bimodal regulation. This unique bimodal DDR may provide a strategy for survival and plasticity in an ever-changing environment. Supported by RO1 and supplement from the NIH Institute of General Medicine to V.G. Godoy },
    author = {Ching, Carly and Godoy, Veronica},
    doi = {10.1096/fasebj.29.1_supplement.879.15},
    journal = {The FASEB Journal},
    number = {1{\_}supplement},
    pages = {879.15},
    title = {{Insights into the mechanism regulating the DNA Damage Response in Acinetobacter baumannii}},
    url = {https://www.fasebj.org/doi/abs/10.1096/fasebj.29.1{\_}supplement.879.15},
    volume = {29},
    year = {2015}
    }
  • [DOI] R. B. Rosengaus, K. F. Schultheis, A. Yalonetskaya, M. S. Bulmer, W. S. DuComb, R. W. Benson, J. P. Thottam, and V. Godoy-Carter, “Symbiont-derived $\beta$-1,3-glucanases in a social insect: Mutualism beyond nutrition,” Frontiers in microbiology, 2014.
    [Bibtex]
    @article{Rosengaus2014,
    abstract = {Termites have had a long co-evolutionary history with prokaryotic and eukaryotic gut microbes. Historically, the role of these anaerobic obligate symbionts has been attributed to the nutritional welfare of the host. We provide evidence that protozoa (and/or their associated bacteria) colonizing the hindgut of the dampwood termite Zootermopsis angusticollis, synthesize multiple functional $\beta$-1,3-glucanases, enzymes known for breaking down $\beta$-1,3-glucans, the main component of fungal cell walls.These enzymes, we propose, may help in both digestion of ingested fungal hyphae and protection against invasion by fungal pathogens.This research points to an additional novel role for the mutualistic hindgut microbial consortia of termites, an association that may extend beyond lignocellulolytic activity and nitrogen fixation to include a reduction in the risks of mycosis at both the individual- and colony-levels while nesting in and feeding on microbial-rich decayed wood.},
    author = {Rosengaus, Rebeca B. and Schultheis, Kelley F. and Yalonetskaya, Alla and Bulmer, Mark S. and DuComb, William S. and Benson, Ryan W. and Thottam, John P. and Godoy-Carter, Veronica},
    doi = {10.3389/fmicb.2014.00607},
    isbn = {1664-302X},
    issn = {1664302X},
    journal = {Frontiers in Microbiology},
    keywords = {3-glucanases,Disease resistance,Gut protozoa,Mycosis,Social immunity,Termites,$\beta$-1},
    pmid = {25484878},
    title = {{Symbiont-derived $\beta$-1,3-glucanases in a social insect: Mutualism beyond nutrition}},
    year = {2014}
    }
  • [DOI] R. W. Benson, T. M. Cafarelli, T. J. Rands, I. Lin, and V. G. Godoy, “Selection of dinB alleles suppressing survival loss upon dinB overexpression in Escherichia coli,” Journal of bacteriology, 2014.
    [Bibtex]
    @article{Benson2014,
    abstract = {Escherichia coli strains overproducing DinB undergo survival loss; however, the mechanisms regulating this phenotype are poorly understood. Here we report a genetic selection revealing DinB residues essential to effect this loss-of-survival phenotype. The selection uses strains carrying both an antimutator allele of DNA polymerase III (Pol III) $\alpha$-subunit (dnaE915) and either chromosomal or plasmid-borne dinB alleles. We hypothesized that dnaE915 cells would respond to DinB overproduction differently from dnaE(+) cells because the dnaE915 allele is known to have an altered genetic interaction with dinB(+) compared to its interaction with dnaE(+). Notably, we observe a loss-of-survival phenotype in dnaE915 strains with either a chromosomal catalytically inactive dinB(D103N) allele or a low-copy-number plasmid-borne dinB(+) upon DNA damage treatment. Furthermore, we find that the loss-of-survival phenotype occurs independently of DNA damage treatment in a dnaE915 strain expressing the catalytically inactive dinB(D103N) allele from a low-copy-number plasmid. The selective pressure imposed resulted in suppressor mutations that eliminated growth defects. The dinB intragenic mutations examined were either base pair substitutions or those that we inferred to be loss of function (i.e., deletions and insertions). Further analyses of selected novel dinB alleles, generated by single-base-pair substitutions in the dnaE915 strain, indicated that these no longer effect loss of survival upon overproduction in dnaE(+) strains. These mutations are mapped to specific areas of DinB; this permits us to gain insights into the mechanisms underlying the DinB-mediated overproduction loss-of-survival phenotype.},
    author = {Benson, Ryan W. and Cafarelli, Tiziana M. and Rands, Thomas J. and Lin, Ida and Godoy, Veronica G.},
    doi = {10.1128/JB.01782-14},
    issn = {10985530},
    journal = {Journal of Bacteriology},
    pmid = {24914188},
    title = {{Selection of dinB alleles suppressing survival loss upon dinB overexpression in Escherichia coli}},
    year = {2014}
    }
  • [DOI] T. M. Cafarelli, T. J. Rands, and V. G. Godoy, “The DinB•RecA complex of \textlessi\textgreaterEscherichia coli\textless/i\textgreater mediates an efficient and high-fidelity response to ubiquitous alkylation lesions,” Environmental and molecular mutagenesis, vol. 55, iss. 2, p. 92–102, 2014.
    [Bibtex]
    @article{Cafarelli2014,
    abstract = {Alkylation DNA lesions are ubiquitous, and result from normal cellular metabolism as well as from treatment with methylating agents and chemotherapeutics. DNA damage tolerance by translesion synthesis DNA polymerases has an important role in cellular resistance to alkylating agents. However, it is not yet known whether Escherichia coli (E. coli) DNA Pol IV (DinB) alkylation lesion bypass efficiency and fidelity in vitro are similar to those inferred by genetic analyses. We hypothesized that DinB-mediated bypass of 3-deaza-3-methyladenine, a stable analog of 3-methyladenine, the primary replication fork-stalling alkylation lesion, would be of high fidelity. We performed here the first kinetic analyses of E. coli DinB•RecA binary complexes. Whether alone or in a binary complex, DinB inserted the correct deoxyribonucleoside triphosphate (dNTP) opposite either lesion-containing or undamaged template; the incorporation of other dNTPs was largely inefficient. DinB prefers undamaged DNA, but the DinB•RecA binary complex increases its catalytic efficiency on lesion-containing template, perhaps as part of a regulatory mechanism to better respond to alkylation damage. Notably, we find that a DinB derivative with enhanced affinity for RecA, either alone or in a binary complex, is less efficient and has a lower fidelity than DinB or DinB•RecA. This finding contrasts our previous genetic analyses. Therefore, mutagenesis resulting from alkylation lesions is likely limited in cells by the activity of DinB•RecA. These two highly conserved proteins play an important role in maintaining genomic stability when cells are faced with ubiquitous DNA damage. Kinetic analyses are important to gain insights into the mechanism(s) regulating TLS DNA polymerases.},
    author = {Cafarelli, Tiziana M. and Rands, Thomas J. and Godoy, Veronica G.},
    doi = {10.1002/em.21826},
    issn = {08936692},
    journal = {Environmental and Molecular Mutagenesis},
    keywords = {DNA replication,Escherichia coli,enzyme kinetics,mutagenesis,nucleotide,protein complexes},
    month = {mar},
    number = {2},
    pages = {92--102},
    pmid = {24243543},
    title = {{The DinB•RecA complex of {\textless}i{\textgreater}Escherichia coli{\textless}/i{\textgreater} mediates an efficient and high-fidelity response to ubiquitous alkylation lesions}},
    url = {http://www.ncbi.nlm.nih.gov/pubmed/24243543 http://doi.wiley.com/10.1002/em.21826},
    volume = {55},
    year = {2014}
    }
  • [DOI] A. E. Macguire, M. C. Ching, B. H. Diamond, A. Kazakov, P. Novichkov, and V. G. Godoy, “Activation of phenotypic subpopulations in response to ciprofloxacin treatment in Acinetobacter baumannii.,” Molecular microbiology, vol. 92, iss. 1, p. 138–52, 2014.
    [Bibtex]
    @article{Macguire2014,
    abstract = {The multidrug-resistant, opportunistic pathogen, Acinetobacter baumannii, has spread swiftly through hospitals worldwide. Previously, we demonstrated that A. baumannii regulates the expression of various genes in response to DNA damage. Some of these regulated genes, especially those encoding the multiple error-prone DNA polymerases, can be implicated in induced mutagenesis, leading to antibiotic resistance. Here, we further explore the DNA damage-inducible system at the single cell level using chromosomal transcriptional reporters for selected DNA damage response genes. We found the genes examined respond in a bimodal fashion to ciprofloxacin treatment, forming two phenotypic subpopulations: induced and uninduced. This bimodal response to ciprofloxacin treatment in A. baumannii is unique and quite different than the Escherichia coli paradigm. The subpopulations are not genetically different, with each subpopulation returning to a starting state and differentiating with repeated treatment. We then identified a palindromic motif upstream of certain DNA damage response genes, and have shown alterations to this sequence to diminish the bimodal induction in response to DNA damaging treatment. Lastly, we are able to show a biological advantage for a bimodal response, finding that one subpopulation survives ciprofloxacin treatment better than the other.},
    author = {Macguire, Ashley E and Ching, Meining Carly and Diamond, Brett H and Kazakov, Alexey and Novichkov, Pavel and Godoy, Veronica G},
    doi = {10.1111/mmi.12541},
    file = {:Users/merlin/Library/Application Support/Mendeley Desktop/Downloaded/Macguire et al. - 2014 - Activation of phenotypic subpopulations in response to ciprofloxacin treatment in Acinetobacter baumannii(2).pdf:pdf},
    issn = {1365-2958},
    journal = {Molecular microbiology},
    month = {apr},
    number = {1},
    pages = {138--52},
    pmid = {24612352},
    publisher = {NIH Public Access},
    title = {{Activation of phenotypic subpopulations in response to ciprofloxacin treatment in Acinetobacter baumannii.}},
    url = {http://www.ncbi.nlm.nih.gov/pubmed/24612352 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4005408},
    volume = {92},
    year = {2014}
    }
  • [DOI] A. E. MacGuire, M. C. Ching, B. H. Diamond, A. Kazakov, P. Novichkov, and V. G. Godoy, “Activation of phenotypic subpopulations in response to ciprofloxacin treatment in \textlessi\textgreaterA\textless/i\textgreater \textlessi\textgreatercinetobacter baumannii\textless/i\textgreater,” Molecular microbiology, vol. 92, iss. 1, p. 138–152, 2014.
    [Bibtex]
    @article{MacGuire2014,
    author = {MacGuire, Ashley E. and Ching, Meining Carly and Diamond, Brett H. and Kazakov, Alexey and Novichkov, Pavel and Godoy, Veronica G.},
    doi = {10.1111/mmi.12541},
    file = {:Users/merlin/Library/Application Support/Mendeley Desktop/Downloaded/MacGuire et al. - 2014 - Activation of phenotypic subpopulations in response to ciprofloxacin treatment in iAi icinetobacter baumanniii.pdf:pdf},
    issn = {0950382X},
    journal = {Molecular Microbiology},
    month = {apr},
    number = {1},
    pages = {138--152},
    publisher = {John Wiley {\&} Sons, Ltd},
    title = {{Activation of phenotypic subpopulations in response to ciprofloxacin treatment in {\textless}i{\textgreater}A{\textless}/i{\textgreater} {\textless}i{\textgreater}cinetobacter baumannii{\textless}/i{\textgreater}}},
    url = {http://doi.wiley.com/10.1111/mmi.12541},
    volume = {92},
    year = {2014}
    }
  • [DOI] R. B. Rosengaus, K. F. Schultheis, A. Yalonetskaya, M. S. Bulmer, W. S. DuComb, R. W. Benson, J. P. Thottam, and V. Godoy-Carter, “Symbiont-derived β-1,3-glucanases in a social insect: mutualism beyond nutrition,” Frontiers in microbiology, vol. 5, p. 607, 2014.
    [Bibtex]
    @article{Rosengaus2014a,
    abstract = {Termites have had a long co-evolutionary history with prokaryotic and eukaryotic gut microbes. Historically, the role of these anaerobic obligate symbionts has been attributed to the nutritional welfare of the host. We provide evidence that protozoa (and/or their associated bacteria) colonizing the hindgut of the dampwood termite Zootermopsis angusticollis, synthesize multiple functional beta-1,3-glucanases, enzymes known for breaking down beta-1,3-glucans, the main component of fungal cell walls. These enzymes, we propose, may help in both digestion of ingested fungal hyphae and protection against invasion by fungal pathogens. This research points to an additional novel role for the mutualistic hindgut microbial consortia of termites, an association that may extend beyond ligno-cellulolytic activity and nitrogen fixation to include a reduction in the risks of mycosis at both the individual- and colony-levels while nesting in and feeding on microbial-rich decayed wood.},
    author = {Rosengaus, Rebeca B. and Schultheis, Kelley F. and Yalonetskaya, Alla and Bulmer, Mark S. and DuComb, William S. and Benson, Ryan W. and Thottam, John P. and Godoy-Carter, Veronica},
    doi = {10.3389/fmicb.2014.00607},
    file = {:Users/merlin/Library/Application Support/Mendeley Desktop/Downloaded/Rosengaus et al. - 2014 - Symbiont-derived {\^{I}}²-1,3-glucanases in a social insect mutualism beyond nutrition.pdf:pdf},
    issn = {1664-302X},
    journal = {Frontiers in Microbiology},
    keywords = {Disease Resistance,Social immunity,glucanases,gut protozoa,mycosis,termites},
    month = {nov},
    pages = {607},
    publisher = {Frontiers},
    title = {{Symbiont-derived {\^{I}}²-1,3-glucanases in a social insect: mutualism beyond nutrition}},
    url = {http://journal.frontiersin.org/article/10.3389/fmicb.2014.00607/abstract},
    volume = {5},
    year = {2014}
    }
  • [DOI] M. D. Norton, A. J. Spilkia, and V. G. Godoy, “Antibiotic resistance acquired through a DNA damage-inducible response in Acinetobacter baumannii,” Journal of bacteriology, 2013.
    [Bibtex]
    @article{Norton2013,
    abstract = {Acinetobacter baumannii is an emerging nosocomial, opportunistic pathogen that survives desiccation and quickly acquires resistance to multiple antibiotics. Escherichia coli gains antibiotic resistances by expressing genes involved in a global response to DNA damage. Therefore, we asked whether A. baumannii does the same through a yet undetermined DNA damage response akin to the E. coli paradigm. We found that recA and all of the multiple error-prone DNA polymerase V (Pol V) genes, those organized as umuDC operons and unlinked, are induced upon DNA damage in a RecA-mediated fashion. Consequently, we found that the frequency of rifampin-resistant (Rif(r)) mutants is dramatically increased upon UV treatment, alkylation damage, and desiccation, also in a RecA-mediated manner. However, in the recA insertion knockout strain, in which we could measure the recA transcript, we found that recA was induced by DNA damage, while uvrA and one of the unlinked umuC genes were somewhat derepressed in the absence of DNA damage. Thus, the mechanism regulating the A. baumannii DNA damage response is likely different from that in E. coli. Notably, it appears that the number of DNA Pol V genes may directly contribute to desiccation-induced mutagenesis. Sequences of the rpoB gene from desiccation-induced Rif(r) mutants showed a signature that was consistent with E. coli DNA polymerase V-generated base-pair substitutions and that matched that of sequenced A. baumannii clinical Rif(r) isolates. These data strongly support an A. baumannii DNA damage-inducible response that directly contributes to antibiotic resistance acquisition, particularly in hospitals where A. baumannii desiccates and tenaciously survives on equipment and surfaces.},
    author = {Norton, Matthew D. and Spilkia, Allison J. and Godoy, Veronica G.},
    doi = {10.1128/JB.02176-12},
    isbn = {1098-5530 (Electronic)$\backslash$r0021-9193 (Linking)},
    issn = {00219193},
    journal = {Journal of Bacteriology},
    pmid = {23316046},
    title = {{Antibiotic resistance acquired through a DNA damage-inducible response in Acinetobacter baumannii}},
    year = {2013}
    }
  • [DOI] R. B. Rosengaus, K. Mead, W. S. {Du Comb}, R. W. Benson, and V. G. Godoy, “Nest sanitation through defecation: Antifungal properties of wood cockroach feces,” Naturwissenschaften, 2013.
    [Bibtex]
    @article{Rosengaus2013,
    abstract = {The wood cockroach Cryptocercus punctulatus nests as family units inside decayed wood, a substrate known for its high microbial load. We tested the hypothesis that defecation within their nests, a common occurrence in this species, reduces the probability of fungal development. Conidia of the entomopathogenic fungus, Metarhizium anisopliae, were incubated with crushed feces and subsequently plated on potato dextrose agar. Relative to controls, the viability of fungal conidia was significantly reduced following incubation with feces and was negatively correlated with incubation time. Although the cockroach's hindgut contained abundant $\beta$-1,3-glucanase activity, its feces had no detectable enzymatic function. Hence, these enzymes are unlikely the source of the fungistasis. Instead, the antifungal compound(s) of the feces involved heat-sensitive factor(s) of potential microbial origin. When feces were boiled or when they were subjected to ultraviolet radiation and subsequently incubated with conidia, viability was "rescued" and germination rates were similar to those of controls. Filtration experiments indicate that the fungistatic activity of feces results from chemical interference. Because Cryptocercidae cockroaches have been considered appropriate models to make inferences about the factors fostering the evolution of termite sociality, we suggest that nesting in microbe-rich environments likely selected for the coupling of intranest defecation and feces fungistasis in the common ancestor of wood cockroaches and termites. This might in turn have served as a preadaptation that prevented mycosis as these phylogenetically related taxa diverged and evolved respectively into subsocial and eusocial organizations.},
    author = {Rosengaus, Rebeca B. and Mead, Kerry and {Du Comb}, William S. and Benson, Ryan W. and Godoy, Veronica G.},
    doi = {10.1007/s00114-013-1110-x},
    isbn = {0011401311},
    issn = {00281042},
    journal = {Naturwissenschaften},
    keywords = {Cryptocercus punctulatus,Metarhizium anisopliae,Preadaptation,Sociality,Termites,$\beta$-1,3-Glucanases},
    pmid = {24271031},
    title = {{Nest sanitation through defecation: Antifungal properties of wood cockroach feces}},
    year = {2013}
    }
  • [DOI] T. M. Cafarelli, T. J. Rands, R. W. Benson, P. A. Rudnicki, I. Lin, and V. G. Godoy, “A Single Residue Unique to DinB-Like Proteins Limits Formation of the Polymerase IV Multiprotein Complex in Escherichia coli,” Journal of bacteriology, vol. 195, iss. 6, p. 1179–1193, 2013.
    [Bibtex]
    @article{Cafarelli2013,
    abstract = {The activity of DinB is governed by the formation of a multiprotein complex (MPC) with RecA and UmuD. We identified two highly conserved surface residues in DinB, cysteine 66 (C66) and proline 67 (P67). Mapping on the DinB tertiary structure suggests these are noncatalytic, and multiple-sequence alignments indicate that they are unique among DinB-like proteins. To investigate the role of the C66-containing surface in MPC formation, we constructed the dinB(C66A) derivative. We found that DinB(C66A) copurifies with its interacting partners, RecA and UmuD, to a greater extent than DinB. Notably, copurification of RecA with DinB is somewhat enhanced in the absence of UmuD and is further increased for DinB(C66A). In vitro pulldown assays also indicate that DinB(C66A) binds RecA and UmuD better than DinB. We note that the increased affinity of DinB(C66A) for UmuD is RecA dependent. Thus, the C66-containing binding surface appears to be critical to modulate interaction with UmuD, and particularly with RecA. Expression of dinB(C66A) from the chromosome resulted in detectable differences in dinB-dependent lesion bypass fidelity and homologous recombination. Study of this DinB derivative has revealed a key surface on DinB, which appears to modulate the strength of MPC binding, and has suggested a binding order of RecA and UmuD to DinB. These findings will ultimately permit the manipulation of these enzymes to deter bacterial antibiotic resistance acquisition and to gain insights into cancer development in humans.},
    author = {Cafarelli, T. M. and Rands, T. J. and Benson, R. W. and Rudnicki, P. A. and Lin, I. and Godoy, V. G.},
    doi = {10.1128/JB.01349-12},
    issn = {0021-9193},
    journal = {Journal of Bacteriology},
    month = {mar},
    number = {6},
    pages = {1179--1193},
    pmid = {23292773},
    title = {{A Single Residue Unique to DinB-Like Proteins Limits Formation of the Polymerase IV Multiprotein Complex in Escherichia coli}},
    url = {http://www.ncbi.nlm.nih.gov/pubmed/23292773 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3592004 http://jb.asm.org/cgi/doi/10.1128/JB.01349-12},
    volume = {195},
    year = {2013}
    }
  • [DOI] R. W. Benson, T. M. Cafarelli, and V. G. Godoy, “SOE-LRed: A simple and time-efficient method to localize genes with point mutations onto the Escherichia coli chromosome,” Journal of microbiological methods, 2011.
    [Bibtex]
    @article{Benson2011,
    abstract = {We use a powerful method to replace wild-type genes on the chromosome of Escherichia coli. Using a unique form of PCR, we generate easily constructible gene fusions bearing single point mutations. Used in conjunction with homologous recombination, this method eliminates cloning procedures previously used for this purpose. {\textcopyright} 2010 Elsevier B.V.},
    archivePrefix = {arXiv},
    arxivId = {NIHMS150003},
    author = {Benson, Ryan W. and Cafarelli, Tiziana M. and Godoy, Veronica G.},
    doi = {10.1016/j.mimet.2010.12.020},
    eprint = {NIHMS150003},
    isbn = {2122633255},
    issn = {01677012},
    journal = {Journal of Microbiological Methods},
    keywords = {DinB,E. coli,Lambda Red,Point mutation,SOE PCR,Transformation},
    pmid = {21185880},
    title = {{SOE-LRed: A simple and time-efficient method to localize genes with point mutations onto the Escherichia coli chromosome}},
    year = {2011}
    }
  • [DOI] R. W. Benson, M. D. Norton, I. Lin, W. S. du Comb, and V. G. Godoy, “An active site aromatic triad in escherichia coli DNA pol IV coordinates cell survival and mutagenesis in different DNA damaging agents,” Plos one, 2011.
    [Bibtex]
    @article{Benson2011a,
    abstract = {DinB (DNA Pol IV) is a translesion (TLS) DNA polymerase, which inserts a nucleotide opposite an otherwise replication-stalling N(2)-dG lesion in vitro, and confers resistance to nitrofurazone (NFZ), a compound that forms these lesions in vivo. DinB is also known to be part of the cellular response to alkylation DNA damage. Yet it is not known if DinB active site residues, in addition to aminoacids involved in DNA synthesis, are critical in alkylation lesion bypass. It is also unclear which active site aminoacids, if any, might modulate DinB's bypass fidelity of distinct lesions. Here we report that along with the classical catalytic residues, an active site "aromatic triad", namely residues F12, F13, and Y79, is critical for cell survival in the presence of the alkylating agent methyl methanesulfonate (MMS). Strains expressing dinB alleles with single point mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in addition to its role in TLS, modulates DinB's accuracy in bypassing distinct lesions. The high bypass fidelity of prevalent alkylation lesions is evident even when the DinB active site performs error-prone NFZ-induced lesion bypass. The analyses carried out with the active site aromatic triad suggest that the DinB active site residues are poised to proficiently bypass distinctive DNA lesions, yet they are also malleable so that the accuracy of the bypass is lesion-dependent.},
    author = {Benson, Ryan W. and Norton, Matthew D. and Lin, Ida and du Comb, William S. and Godoy, Veronica G.},
    doi = {10.1371/journal.pone.0019944},
    isbn = {1932-6203 (Electronic)$\backslash$r1932-6203 (Linking)},
    issn = {19326203},
    journal = {PLoS ONE},
    pmid = {21614131},
    title = {{An active site aromatic triad in escherichia coli DNA pol IV coordinates cell survival and mutagenesis in different DNA damaging agents}},
    year = {2011}
    }
  • [DOI] R. W. Benson, T. M. Cafarelli, and V. G. Godoy, “SOE-LRed: A simple and time-efficient method to localize genes with point mutations onto the Escherichia coli chromosome,” Journal of microbiological methods, vol. 84, iss. 3, p. 479–481, 2011.
    [Bibtex]
    @article{Benson2011b,
    abstract = {We use a powerful method to replace wild-type genes on the chromosome of Escherichia coli. Using a unique form of PCR, we generate easily constructible gene fusions bearing single point mutations. Used in conjunction with homologous recombination, this method eliminates cloning procedures previously used for this purpose.},
    author = {Benson, Ryan W. and Cafarelli, Tiziana M. and Godoy, Veronica G.},
    doi = {10.1016/j.mimet.2010.12.020},
    issn = {01677012},
    journal = {Journal of Microbiological Methods},
    month = {mar},
    number = {3},
    pages = {479--481},
    pmid = {21185880},
    title = {{SOE-LRed: A simple and time-efficient method to localize genes with point mutations onto the Escherichia coli chromosome}},
    url = {http://www.ncbi.nlm.nih.gov/pubmed/21185880 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3045631 https://linkinghub.elsevier.com/retrieve/pii/S0167701210004513},
    volume = {84},
    year = {2011}
    }
  • [DOI] S. E. Cohen, V. G. Godoy, and G. C. Walker, “Transcriptional modulator nusA interacts with translesion DNA polymerases in escherichia coli,” Journal of bacteriology, 2009.
    [Bibtex]
    @article{Cohen2009,
    abstract = {NusA, a modulator of RNA polymerase, interacts with the DNA polymerase DinB. An increased level of expression of dinB or umuDC suppresses the temperature sensitivity of the nusA11 strain, requiring the catalytic activities of these proteins. We propose that NusA recruits translesion DNA synthesis (TLS) polymerases to RNA polymerases stalled at gaps, coupling TLS to transcription.},
    author = {Cohen, Susan E. and Godoy, Veronica G. and Walker, Graham C.},
    doi = {10.1128/JB.00941-08},
    isbn = {1098-5530 (Electronic)$\backslash$r0021-9193 (Linking)},
    issn = {00219193},
    journal = {Journal of Bacteriology},
    pmid = {18996995},
    title = {{Transcriptional modulator nusA interacts with translesion DNA polymerases in escherichia coli}},
    year = {2009}
    }
  • [DOI] K. Lewis, S. Epstein, V. G. Godoy, and S. H. Hong, Intact DNA in ancient permafrost, 2008.
    [Bibtex]
    @misc{Lewis2008,
    abstract = {Contrary to the generally held notions about microbial survival, the recently published paper by Johnson et al., 'Ancient bacteria show evidence of DNA repair', presents evidence suggesting that non-spore-forming bacteria in ancient samples are apparently alive, as judged by intact DNA, and fare better than spores. The data presented in this work raise intriguing questions about the nature of bacteria in many of the ancient samples reported to date: are they spores, persisters, sessile vegetative cells or do they make up a slow-growing population? {\textcopyright} 2008 Elsevier Ltd. All rights reserved.},
    author = {Lewis, Kim and Epstein, Slava and Godoy, Veronica G. and Hong, Sun Hee},
    booktitle = {Trends in Microbiology},
    doi = {10.1016/j.tim.2008.01.002},
    isbn = {0966-842X (Print)
    0966-842X (Linking)},
    issn = {0966842X},
    pmid = {18291656},
    title = {{Intact DNA in ancient permafrost}},
    year = {2008}
    }
  • [DOI] V. G. Godoy, D. F. Jarosz, S. M. Simon, A. Abyzov, V. Ilyin, and G. C. Walker, “UmuD and RecA Directly Modulate the Mutagenic Potential of the Y Family DNA Polymerase DinB,” Molecular cell, 2007.
    [Bibtex]
    @article{Godoy2007,
    abstract = {DinB is the only translesion Y family DNA polymerase conserved among bacteria, archaea, and eukaryotes. DinB and its orthologs possess a specialized lesion bypass function but also display potentially deleterious -1 frameshift mutagenic phenotypes when overproduced. We show that the DNA damage-inducible proteins UmuD2and RecA act in concert to modulate this mutagenic activity. Structural modeling suggests that the relatively open active site of DinB is enclosed by interaction with these proteins, thereby preventing the template bulging responsible for -1 frameshift mutagenesis. Intriguingly, residues that define the UmuD2-interacting surface on DinB statistically covary throughout evolution, suggesting a driving force for the maintenance of a regulatory protein-protein interaction at this site. Together, these observations indicate that proteins like RecA and UmuD2may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution. {\textcopyright} 2007 Elsevier Inc. All rights reserved.},
    archivePrefix = {arXiv},
    arxivId = {NIHMS150003},
    author = {Godoy, Veronica G. and Jarosz, Daniel F. and Simon, Sharotka M. and Abyzov, Alexej and Ilyin, Valentin and Walker, Graham C.},
    doi = {10.1016/j.molcel.2007.10.025},
    eprint = {NIHMS150003},
    isbn = {1097-2765 (Print)$\backslash$r1097-2765 (Linking)},
    issn = {10972765},
    journal = {Molecular Cell},
    keywords = {DNA,MICROBIO},
    pmid = {18158902},
    title = {{UmuD and RecA Directly Modulate the Mutagenic Potential of the Y Family DNA Polymerase DinB}},
    year = {2007}
    }
  • [DOI] D. F. Jarosz, V. G. Godoy, and G. C. Walker, Proficient and accurate bypass of persistent DNA lesions by DinB DNA polymerases, 2007.
    [Bibtex]
    @misc{Jarosz2007,
    abstract = {Despite nearly universal conservation through evolution, the precise function of the DinB/pol kappa branch of the Y-family of DNA polymerases has remained unclear. Recent results suggest that DinB orthologs from all domains of life proficiently bypass replication blocking lesions that may be recalcitrant to DNA repair mechanisms. Like other translesion DNA polymerases, the error frequency of DinB and its orthologs is higher than the DNA polymerases that replicate the majority of the genome. However, recent results suggest that some Y-family polymerases, including DinB and pol kappa, bypass certain types of DNA damage with greater proficiency than an undamaged template. Moreover, they do so relatively accurately. The ability to employ this mechanism to manage DNA damage may be especially important for types of DNA modification that elude repair mechanisms. For these lesions, translesion synthesis may represent a more important line of defense than for other types of DNA damage that are more easily dealt with by other more accurate mechanisms.},
    author = {Jarosz, Daniel F. and Godoy, Veronica G. and Walker, Graham C.},
    booktitle = {Cell Cycle},
    doi = {10.4161/cc.6.7.4065},
    isbn = {1551-4005 (Electronic)},
    issn = {15514005},
    keywords = {DNA Damage,DinB,Mutagenesis,Pol $\kappa$,Polymerase,XP-V},
    pmid = {17377496},
    title = {{Proficient and accurate bypass of persistent DNA lesions by DinB DNA polymerases}},
    year = {2007}
    }
  • [DOI] D. F. Jarosz, V. G. Godoy, J. C. Delaney, J. M. Essigmann, and G. C. Walker, “A single amino acid governs enhanced activity of DinB DNA polymerases on damaged templates,” Nature, 2006.
    [Bibtex]
    @article{Jarosz2006,
    abstract = {Translesion synthesis (TLS) by Y-family DNA polymerases is a chief mechanism of DNA damage tolerance. Such TLS can be accurate or error-prone, as it is for bypass of a cyclobutane pyrimidine dimer by DNA polymerase eta (XP-V or Rad30) or bypass of a (6-4) TT photoproduct by DNA polymerase V (UmuD'2C), respectively. Although DinB is the only Y-family DNA polymerase conserved among all domains of life, the biological rationale for this striking conservation has remained enigmatic. Here we report that the Escherichia coli dinB gene is required for resistance to some DNA-damaging agents that form adducts at the N2-position of deoxyguanosine (dG). We show that DinB (DNA polymerase IV) catalyses accurate TLS over one such N2-dG adduct (N2-furfuryl-dG), and that DinB and its mammalian orthologue, DNA polymerase kappa, insert deoxycytidine (dC) opposite N2-furfuryl-dG with 10-15-fold greater catalytic proficiency than opposite undamaged dG. We also show that mutating a single amino acid, the 'steric gate' residue of DinB (Phe13 --{\textgreater} Val) and that of its archaeal homologue Dbh (Phe12 --{\textgreater} Ala), separates the abilities of these enzymes to perform TLS over N2-dG adducts from their abilities to replicate an undamaged template. We propose that DinB and its orthologues are specialized to catalyse relatively accurate TLS over some N2-dG adducts that are ubiquitous in nature, that lesion bypass occurs more efficiently than synthesis on undamaged DNA, and that this specificity may be achieved at least in part through a lesion-induced conformational change.},
    author = {Jarosz, Daniel F. and Godoy, Veronica G. and Delaney, James C. and Essigmann, John M. and Walker, Graham C.},
    doi = {10.1038/nature04318},
    isbn = {1476-4687 (Electronic)$\backslash$r0028-0836 (Linking)},
    issn = {14764687},
    journal = {Nature},
    pmid = {16407906},
    title = {{A single amino acid governs enhanced activity of DinB DNA polymerases on damaged templates}},
    year = {2006}
    }
  • [DOI] V. G. Godoy, D. F. Jarosz, F. L. Walker, L. A. Simmons, and G. C. Walker, “Y-family DNA polymerases respond to DNA damage-independent inhibition of replication fork progression,” Embo journal, 2006.
    [Bibtex]
    @article{Godoy2006,
    abstract = {In Escherichia coli, the Y-family DNA polymerases Pol IV (DinB) and Pol V (UmuD2'C) enhance cell survival upon DNA damage by bypassing replication-blocking DNA lesions. We report a unique function for these polymerases when DNA replication fork progression is arrested not by exogenous DNA damage, but with hydroxyurea (HU), thereby inhibiting ribonucleotide reductase, and bringing about damage-independent DNA replication stalling. Remarkably, the umuC122::Tn5 allele of umuC, dinB, and certain forms of umuD gene products endow E. coli with the ability to withstand HU treatment (HUR). The catalytic activities of the UmuC122 and DinB proteins are both required for HUR. Moreover, the lethality brought about by such stalled replication forks in the wild-type derivatives appears to proceed through the toxin/antitoxin pairs mazEF and relBE. This novel function reveals a role for Y-family polymerases in enhancing cell survival under conditions of nucleotide starvation, in addition to their established functions in response to DNA damage.},
    author = {Godoy, Veronica G. and Jarosz, Daniel F. and Walker, Fabienne L. and Simmons, Lyle A. and Walker, Graham C.},
    doi = {10.1038/sj.emboj.7600986},
    isbn = {0261-4189 (Print)$\backslash$r0261-4189 (Linking)},
    issn = {02614189},
    journal = {EMBO Journal},
    keywords = {DinB,Hydroxyurea,UmuC,UmuD,mazEF},
    pmid = {16482223},
    title = {{Y-family DNA polymerases respond to DNA damage-independent inhibition of replication fork progression}},
    year = {2006}
    }
  • [DOI] P. J. Beuning, S. M. Simon, V. G. Godoy, D. F. Jarosz, and G. C. Walker, Characterization of Escherichia coli Translesion Synthesis Polymerases and Their Accessory Factors, 2006.
    [Bibtex]
    @misc{Beuning2006,
    abstract = {Members of the Y family of DNA polymerases are specialized to replicate lesion-containing DNA. However, they lack 3′-5′ exonuclease activity and have reduced fidelity compared to replicative polymerases when copying undamaged templates, and thus are potentially mutagenic. Y family polymerases must be tightly regulated to prevent aberrant mutations on undamaged DNA while permitting replication only under conditions of DNA damage. These polymerases provide a mechanism of DNA damage tolerance, confer cellular resistance to a variety of DNA-damaging agents, and have been implicated in bacterial persistence. The Y family polymerases are represented in all domains of life. Escherichia coli possesses two members of the Y family, DNA pol IV (DinB) and DNA pol V (UmuD′2C), and several regulatory factors, including those encoded by the umuD gene that influence the activity of UmuC. This chapter outlines procedures for in vivo and in vitro analysis of these proteins. Study of the E. coli Y family polymerases and their accessory factors is important for understanding the broad principles of DNA damage tolerance and mechanisms of mutagenesis throughout evolution. Furthermore, study of these enzymes and their role in stress-induced mutagenesis may also give insight into a variety of phenomena, including the growing problem of bacterial antibiotic resistance. {\textcopyright} 2006 Elsevier Inc. All rights reserved.},
    author = {Beuning, Penny J. and Simon, Sharotka M. and Godoy, Veronica G. and Jarosz, Daniel F. and Walker, Graham C.},
    booktitle = {Methods in Enzymology},
    doi = {10.1016/S0076-6879(06)08020-7},
    isbn = {0076-6879 (Print)$\backslash$r0076-6879 (Linking)},
    issn = {00766879},
    pmid = {16793378},
    title = {{Characterization of Escherichia coli Translesion Synthesis Polymerases and Their Accessory Factors}},
    year = {2006}
    }
  • [DOI] M. D. Sutton, B. T. Smith, V. G. Godoy, and G. C. Walker, “The SOS Response: Recent Insights into umuDC -Dependent Mutagenesis and DNA,” Annual review genetics, 2000.
    [Bibtex]
    @article{Sutton2000,
    abstract = {Be they prokaryotic or eukaryotic, organisms are exposed to a multitude of deoxyribonucleic acid (DNA) damaging agents ranging from ultraviolet (UV) light to fungal metabolites, like Aflatoxin B1. Furthermore, DNA damaging agents, such as reactive oxygen species, can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an organism's genome. As a result, organisms have evolved a number of vitally important mechanisms to repair DNA damage in a high fidelity manner. They have also evolved systems (cell cycle checkpoints) that delay the resumption of the cell cycle after DNA damage to allow more time for these accurate processes to occur. If a cell cannot repair DNA damage accurately, a mutagenic event may occur. Most bacteria, including Escherichia coli, have evolved a coordinated response to these challenges to the integrity of their genomes. In E. coli, this inducible system is termed the SOS response, and it controls both accurate and potentially mutagenic DNA repair functions [reviewed comprehensively in () and also in ()]. Recent advances have focused attention on the umuD(+)C(+)-dependent, translesion DNA synthesis (TLS) process that is responsible for SOS mutagenesis (). Here we discuss the SOS response of E. coli and concentrate in particular on the roles of the umuD(+)C(+) gene products in promoting cell survival after DNA damage via TLS and a primitive DNA damage checkpoint.},
    author = {Sutton, Mark D and Smith, Bradley T and Godoy, Veronica G and Walker, Graham C},
    doi = {10.1146/annurev.genet.34.1.479},
    isbn = {0066-4197 (Print)},
    issn = {0066-4197},
    journal = {Annual Review Genetics},
    pmid = {11092836},
    title = {{The SOS Response: Recent Insights into umuDC -Dependent Mutagenesis and DNA}},
    year = {2000}
    }
  • V. G. Godoy, F. S. Gizatullin, and M. S. Fox, “Some features of the mutability of bacteria during nonlethal selection.,” Genetics, vol. 154, iss. 1, p. 49–59, 2000.
    [Bibtex]
    @article{Godoy2000,
    abstract = {We describe the mutability of the Trp(-) chromosomal +1 frameshift mutation trpE7999 during nonlethal selection, finding that the appearance of Trp(+) revertants behaves similarly to that of episomal Lac(+) revertants. In addition, we show that a feature of the Lac(+) and Trp(+) mutability is the accumulation of Trp(+) and Lac(+) revertants with additional unselected mutations, most of which are not due to heritable mutators. The cells undergoing nonlethal selection apparently experience an epigenetic change resulting in a subset of bacteria with elevated mutability that often remain hypermutable for the duration of selection. The epigenetic change provoked by nonlethal selection appears to be mediated by a unique function provided by the F'128 episome.},
    author = {Godoy, V G and Gizatullin, F S and Fox, M S},
    issn = {0016-6731},
    journal = {Genetics},
    month = {jan},
    number = {1},
    pages = {49--59},
    pmid = {10628968},
    publisher = {Genetics Society of America},
    title = {{Some features of the mutability of bacteria during nonlethal selection.}},
    url = {http://www.ncbi.nlm.nih.gov/pubmed/10628968 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC1460914},
    volume = {154},
    year = {2000}
    }
  • [DOI] V. G. Godoy and M. S. Fox, “Transposon stability and a role for conjugational transfer in adaptive mutability,” Proceedings of the national academy of sciences, vol. 97, iss. 13, p. 7393–7398, 2000.
    [Bibtex]
    @article{Godoy2000a,
    abstract = {Lac(+) revertants of Escherichia coli that occur after prolonged nonlethal selection display a high frequency of transposon loss when the transposon Tn10 and the reverting lacI33 allele are linked on an F'128 episome. As many as 20{\%} of the Lac(+) revertants are sensitive to tetracycline, about half because of transposon loss, nearly all by precise excision, and the remainder because of amplification of both the transposon and the linked lac allele. Lethality of the amplified products in the presence of tetracycline is a peculiarity of the tetA gene at high gene dosage. The selective conditions on lactose medium result in 10{\%} transposon-free revertants, whether or not a requirement for conjugal DNA transfer is imposed. In addition, a similar fraction, about 5{\%} of Lac(-) unreverted colonies that are products of transfer between cells experiencing nonlethal selection are also tetracycline-sensitive, and all are attributable to loss of the Tn10 transposon. These results suggest the possibility that the high frequency of transposon loss is a consequence of conjugal transfer, making this loss a marker for that transfer. We suggest that conjugal DNA transfer may be a prominent feature in the mutability process that occurs during nonlethal selection and that the subset of bacteria displaying hypermutability are those that experience such transfer.},
    author = {Godoy, V. G. and Fox, M. S.},
    doi = {10.1073/pnas.130186597},
    issn = {0027-8424},
    journal = {Proceedings of the National Academy of Sciences},
    month = {jun},
    number = {13},
    pages = {7393--7398},
    pmid = {10840058},
    title = {{Transposon stability and a role for conjugational transfer in adaptive mutability}},
    url = {http://www.ncbi.nlm.nih.gov/pubmed/10840058 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC16556 http://www.pnas.org/cgi/doi/10.1073/pnas.130186597},
    volume = {97},
    year = {2000}
    }

 

 

 

 

 

 

 

 

 

 

 

Old list

Benson RW, Cafarelli TM, Rands TJ, Lin I, and Godoy VG. (2014). Selection of dinB alleles suppressing survival loss upon dinB overexpression in Escherichia coli. J Bacteriol. 196(16): 3023-3035. PDF

MacGuire AE, Ching MC, Diamond BH, Kazakov A, Novichkov P, and Godoy VG. (2014). Activation of phenotypic subpopulations in response to ciprofloxacin treatment in Acinetobacter baumannii. Mol Microbiol. 92(1): 138-152. PDF

Cafarelli TM, Rands TJ, and Godoy VG. (2014). The DinB•RecA complex of Escherichia coli mediates an efficient and high-fidelity response to ubiquitous alkylation lesions. Environ Mol Mutagen. 55(2): 92-102. PDF

Rosengaus RB, Mead K, Du Comb WS, Benson RW, and Godoy VG. (2013). Nest sanitation through defacation: antifungal properties of wood cockroach feces. Naturwissenschaften. 100 (11): 1051-1059. PDF

Godoy VG, Muirhead A, and Woodruff R. (2013). Features of Escherichia coli mutant colonies appearing on nonlethal conditions of selection. Mol Cancer Biol. In press. PDF

Norton MD, Spilkia AJ, and Godoy VG. (2013). Antibiotic resistance acquired through a DNA damage-inducible response in Acinetobacter baumannii. J Bacteriol. 195(6): 1335-1345. PDF

Cafarelli TM, Rands TJ, Benson RW, Rudnicki PA, Lin I, and Godoy VG. (2013). A single residue unique to DinB-like proteins limits formation of the Pol IV multi-protein complex in Escherichia coli. J Bacteriol. 195(6): 1179-1193. PDF

Benson RW, Norton MD, Lin I, Du Comb WS, Godoy VG. (2011). An active site aromatic triad in Escherichia coli DNA Pol IV coordinates cell survival and mutagenesis in different DNA damaging agents. PLoS ONE 6(5): e19944. doi:10.1371/journal.pone.0019944 PDF

Benson RW*, Cafarelli TM*, Godoy VG. (2011). SOE-LRed: a simple and time-efficient method to localize genes with point mutations onto the Escherichia coli chromosome. J. Microbiol. Methods. 84(3): 479-481. *equally contributing authors PDF

Cohen SE, Godoy VG, Walker GC. (2009). Transcriptional modulator NusA interacts with translesion DNA polymerases in Escherichia coli. J Bacteriol. 191: 665-72. PDF

Godoy, VG, Jarosz, DF, Simon, SM, Abyzov, A, Ilyin, V, and Walker, GC. (2007). UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB. Mol. Cell 28: 1058-1070. PDF

Jarosz DF*, Godoy VG*, Delaney JC, Essigmann JM, Walker GC. (2006). A single amino acid governs enhanced activity of DinB DNA polymerases on damaged templates. Nature 439: 225-228. *equally contributing authors PDF

Godoy VG, Jarosz DF, Walker FL, Simmons LA and Walker GC. (2006). Escherichia coli Y-family DNA polymerases respond to DNA damage-independent inhibition of replication fork progression. EMBO 4: 868-879. PDF

Godoy VG, Beuning P, and Walker GC. (2005). “Gene Expression in Bacterial Systems: The LexA Regulatory System” in Encyclopedia of Biological Chemistry W. J. Lennarz and M. D. Lane, Eds., Academic Press/Elsevier Science, San Diego, CA.

Sutton MD, Smith BT, Godoy VG, Walker GC. (2000). The SOS response: recent insights into umuDC-dependent mutagenesis and DNA damage tolerance. Annu Rev Genet. 34: 479-497. Review. PDF

Godoy VG and Fox MS. (2000). Transposon stability and a role for conjugational transfer in adaptive mutability. Proc Natl Acad Sci USA 13: 7393-7398. PDF

Godoy VG, Gizatullin FS, Fox MS. (2000). Some features of the mutability of bacteria during nonlethal selection. Genetics 154: 49-59. PDF