Researchers identify how RecA protein helps broken DNA find way to bridge the gap

Published on December 14, 2012 at 11:40 PM · No Comments

Every time a human or bacterial cell divides it first must copy its DNA. Specialized proteins unzip the intertwined DNA strands while others follow and build new strands, using the originals as templates. Whenever these proteins encounter a break - and there are many - they stop and retreat, allowing a new cast of molecular players to enter the scene.

Scientists have long sought to understand how one of these players, a repair protein known as RecA in bacterial cells, helps broken DNA find a way to bridge the gap. They knew that RecA guided a broken DNA strand to a matching sequence on an adjoining bit of double-stranded DNA, but they didn't know how. In a new study, researchers report they have identified how the RecA protein does its job.

"The puzzle for scientists has been: How does the damaged DNA look for and find its partner, the matching DNA, so that it can repair itself?" said University of Illinois physics professor Taekjip Ha, who led the study. "Because the genomic DNA is millions of bases long, this task is much like finding a needle in a haystack. We found the answer to how the cell does this so quickly."

The research is described in a paper in eLife, a new open-access journal supported by the Howard Hughes Medical Institute (HHMI), the Max Planck Society and the Wellcome Trust. Ha is an HHMI investigator. The National Science Foundation provided primary funding for this work.

DNA repair is vital to health, vitality and longevity. Disruptions of the process can lead to the early onset of diseases associated with aging or cancer in animals. The breast cancer mutation known as BRCA2, for example, disrupts a gene involved in loading Rad51 (the human equivalent of RecA) onto a broken DNA strand to begin the process of repair.

Previous studies have shown that in bacteria, RecA forms a filament that winds itself around a broken, single strand of DNA. Like a matchmaker trying to find a partner for an unpaired dancer, it scours the corresponding DNA strands for a sequence that will pair up perfectly with the broken strand. Once it finds the sequence, the broken strand steps in and chemically bonds to its new partner, displacing one of the unbroken strands (which eventually pairs with the other broken strand). This elaborate molecular square dance allows the cell to go back to the work of duplicating its genome. Each broken strand now is paired with an unbroken one, and uses the intact strand as a template for replication. (Watch an animation about this process.)

"If a break in DNA occurs, you have to repair it," Ha said. "We wanted to know how RecA helps the DNA find a sequence complementary to it in the sea of genomic DNA, and how it does it so quickly."

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