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Common enzyme is a key player in DNA repair

A quarter century after they discovered it, researchers have identified the job of one of the most common DNA-damage response proteins. The enzyme has puzzled scientists because it is present in nearly every organism, which suggests that it is crucial to life, and yet, in laboratory experiments, its function has remained a mystery.

The discovery suggests that the enigmatic enzyme known as DinB DNA polymerase is specialized for proficient and accurate replication of a particular kind of damaged DNA, reports Graham Walker, an HHMI professor at the Massachusetts Institute of Technology, and his colleagues in the January 12, 2006, issue of the journal Nature. HHMI professors are leading research scientists who received $1 million grants from the Institute to bring innovative teaching to the undergraduate classroom.

DNA is assaulted daily by toxic chemicals, metabolic byproducts, sunlight, and other forms of radiation. Most of the nicks and dings are quickly fixed by the cell's fleet of precision DNA repair processes, which can surgically excise and replace a faulty section.

But sometimes a damaged bit of DNA slips through unrepaired. A faulty nucleotide--the basic constituent of DNA--can stall the temperamental DNA replication machinery as it unwinds and copies the genome in dividing cells. In humans, uncorrected DNA errors passed along to the new daughter cells can lead to cancer.

When DNA integrity is at stake, a family of proteins known as translesion DNA polymerases comes to the rescue. They cannot actually repair a damaged strand of DNA, but they can smooth over the problem by inserting a nucleotide opposite the damaged partner, so the DNA replication machinery can finish duplicating the chromosome despite the damaged DNA. This trick is usually referred to as a DNA damage tolerance mechanism. "It enables the replication to keep going and tolerate the damage, even though it doesn't get rid of it," Walker explained.

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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
11-Jan-2006


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