"Scientists had assumed that as Srs2 moved along the DNA strand, it just pushed off everything in its path," says lead author Edwin Antony, Ph.D., a postdoctoral research associate in biochemistry and molecular biophysics. "This isn't the case - we showed that Srs2 has a specialized structure that allows it to interact specifically with Rad51."

This finding shows how a motor protein like Srs2 can perform the specialized task of remodeling a protein-DNA complex without interference by other similar helicases, he adds.

Because they now know more precisely the nature of this interaction between Srs2 and Rad51, the researchers can narrow their search for drugs that will block DNA repair by Rad51. This type of drug could make a lower dose of a DNA-damaging drug effective in treating cancer.

The research team is now trying to identify the Srs2 homologue in human cells and will study its structure in combination with Rad51. That will allow a more rational approach to understanding how cells cope with DNA damage and how some tumors evade cancer therapeutics, they say.

"In the long-term, my laboratory will look for drug-like molecules that influence this interaction," Ellenberger says. "We are using the Chemical Genetics Screening Center here at the University (htc.wustl). It has vast libraries of molecules that may have the activity we want. Edwin's work on Srs2 and Rad51 will allow us to develop an assay to screen for agents that augment or supersede Srs2's interference with DNA repair."

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