Northeastern University

Good at being bad

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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.


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