Good at being bad

Image by Eliza­Petyton via Flickr

How many things in this world take pride in being bad at their job? It’s cer­tainly not some­thing humans like to brag about, but zoom in to the micro­scopic level and you’ll find that a tiny little piece of us is con­stantly cheer-​​leading its own bad behavior.

It’s an enzyme called an error-​​prone or repair DNA poly­merase and its not very good at its job—DNA syn­thesis . Veronica Godoy-​​Carter thinks it’s the most fas­ci­nating thing around: she’s ded­i­cated her career to under­standing why it is that everything—from bac­teria to yeast to humans—have bad poly­merases and how they’ve man­aged to stick around despite eons of evolution.

So what does it mean for a poly­merase to be good at being bad? First let’s look at replica­tive polymerases–these were dis­cov­ered before their repairing coun­ter­parts and they’re actu­ally quite good at what they do. When DNA needs to be repli­cated, these poly­merases come in and give the DNA a big bear hug, copying what it sees with high fidelity, said Godoy-​​Carter. But with a repair poly­merase, it’s more like a friendly hand­shake instead of a hug — these poly­merases keep their dis­tance and don’t always copy the DNA exactly right. This means they intro­duce muta­tions. In stan­dard pro­ce­dures, this can be very bad.

But it just so hap­pens there are quite a few phys­i­o­log­ical events that rely on failure to be suc­cessful. Sound like an oxy­moron? It’s not. Take antigen recog­ni­tion. In order to develop a new, per­fectly matched anti­body to fight off every­thing from bac­te­rial parts to the flu, cells need to come up with mutated ver­sions of pre-​​existing anti­bodies. They’ll go through thou­sands of random muta­tions until they find one that fits. This, it turns out, is a per­fect job for a repair polymerase.

But what hap­pens when repair poly­merases make mis­takes when they aren’t sup­posed to? This could have impli­ca­tions for cancer, said Godoy-​​Carter. “The cell is playing with fire, here,” she said, “so it is highly reg­u­lated.” A slew of checks and bal­ances are in place to keep the repair poly­merase from slip­ping into set­tings where being bad is actu­ally very bad.