SOS response protein UmuD regulates bacterial DNA replication in response to DNA damage

Abstract

The alpha subunit of DNA polymerase III (DNA pol III) is the main replicative polymerase in Escherichia coli. Because alpha cannot copy damaged DNA, replication is stalled in presence of DNA lesions. To compensate, the cell initiates the SOS response, inducing the expression of at least 57 genes. The products of these genes are involved in DNA damage tolerance mechanisms, one of which is translesion synthesis (TLS), a process by which lesions are bypassed by specialized DNA polymerases with the ability to copy damaged DNA. Full-length UmuD, whose expression is regulated by the SOS response, inhibits DNA replication and prevents mutagenic TLS as part of a primitive DNA damage checkpoint, while the cleaved form UmuD facilitates mutagenesis. It has been suggested that UmuD participates in a primitive DNA damage checkpoint but its exact contribution is still unclear. In order to understand the role of UmuD in regulating DNA replication, the interactions between UmuD and alpha and between UmuD and SSB were investigated, the latter of which is a novel interaction. As a result, we have determined that UmuD disrupts the interaction between alpha and the beta clamp, as well as the interaction between alpha and ssDNA, suggesting a direct role for UmuD in disrupting replication. The UmuD-SSB interaction may contribute to the transition between the replication of undamaged DNA and TLS. Supported by NSF.