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Common enzyme is a key player in DNA repair

ecular building blocks of DNA are adenine, cytosine, guanine, thymine A, C, G, and T in the shorthand of molecular biology. In different combinations, they make up the genes that code for the proteins that carry out the routine and complex tasks necessary for life.

Now, researchers in Walker's lab have discovered that the enzyme DinB is exceptionally skilled at copying over a particular kind of damage to the G nucleotide. When the main DNA replication machinery stalls at the damaged G, the DinB translesion polymerase recognizes the G and adds its chemical partner, C, to form the correct base pair in the new chromosome.

"It was a pretty striking result," Walker said. "Not only did DinB copy over the damaged G nucleotide, it was 10 to 15 times better at copying the damaged G than copying the undamaged G. Up until now, it didn't look like that useful a polymerase."

Experiments led by MIT graduate student Daniel Jarosz and former postdoctoral fellow Veronica Godoy revealed that when bacteria that are missing DinB are exposed to a chemical that causes DNA damage, these bacteria are 1,000 times more likely to die than normal bacteria. Godoy is now an assistant professor of biology at Northeastern University in Boston. She and Jarosz also found that DinB can only repair G damage of a certain size. For example, they said, DinB cannot efficiently copy over a particularly bulky type of damage caused by a chemical found in charcoal-broiled steaks.

The researchers also discovered that a single change in the amino acids that make up DinB will strip it of its unique talent and change it into an ordinary polymerase. When a protein is that easy to modify, scientists assume its function must be important to have survived several billion years of evolution.

"In general, we think that nature evolved this function to help us survive DNA damage that would otherwise kill us," said Walker. "It's probably a kind of damage that all cells encounte
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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
11-Jan-2006


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