Findings shed light on DNA repair mechanism of normal BRCA2

BRCA2 suppresses tumor formation by recruiting and then assisting a protein called RAD51 in repairing damaged DNA, according to a report in the February 10th issue of Nature.

“Due to its large size, it has been difficult to uncover the function of BRCA2,” senior author Dr. Nikola P. Pavletich, from Memorial Sloan-Kettering Cancer Center in New York, told Reuters Health. While the protein was known to play a key role in repairing double-strand breaks (DSBs) in DNA and to interact with RAD51, the precise mechanisms involved were unclear, he added.Using a fungal BRCA2 homologue called Brh2, the researchers show that Brh2 acts at the junction between double-stranded DNA and single-stranded DNA that occurs with DSBs. Brh2 then recruits RAD51 to the site and helps in the formation of the nucleoprotein filament that repairs the damage.”We used the fungal homologue of BRCA2 because the human form is so big and we needed the entire protein to figure out what it does,” Dr. Pavletich said. “But the fungal version has all the hallmarks of the human form, so I think our findings still provide a good indication of what human BRCA2 is doing.”The findings have implications for eventually counteracting the effects of mutated BRCA2. Dr. Pavletich noted that “before we can imagine how to fix something or restore something we have to know how it works. Our findings provide a lot more detail into what exactly BRCA2 does.” (Source: Nature 2005;433:653-657: Reuters Health: Oncolink: February 2005.)