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Publication Detail

Title: Recombination mediator and Rad51 targeting activities of a human BRCA2 polypeptide.

Authors: San Filippo, Joseph; Chi, Peter; Sehorn, Michael G; Etchin, Julia; Krejci, Lumir; Sung, Patrick

Published In J Biol Chem, (2006 Apr 28)

Abstract: BRCA2 likely exerts its tumor suppressor function by enhancing the efficiency of the homology-directed repair of injured chromosomes. To help define the DNA repair role of BRCA2, we expressed and purified a polypeptide, BRC3/4-DBD, that harbors its BRC3 and BRC4 repeats and DNA binding domain. BRC3/4-DBD interacted with hRad51 and bound DNA with a distinct preference for single-stranded (ss) DNA. Importantly we demonstrated by biochemical means and electron microscopy that BRC3/4-DBD nucleates hRad51 onto ssDNA and acts as a recombination mediator in enabling hRad51 to utilize replication protein A-coated ssDNA as recombination substrate. These functions of BRC3/4-DBD required both the BRC repeats and the BRCA2 DNA binding domain. The results thus clarify the role of BRCA2 in Rad51-dependent DNA recombination and repair, and the experimental strategies described herein should be valuable for systematically deciphering this BRCA2 function.

PubMed ID: 16513631 Exiting the NIEHS site

MeSH Terms: BRCA2 Protein/genetics; BRCA2 Protein/metabolism*; DNA Damage; DNA Primers/chemistry; DNA Repair*; DNA, Single-Stranded/genetics; DNA, Single-Stranded/metabolism*; Humans; Peptide Fragments/genetics; Peptide Fragments/metabolism*; Rad51 Recombinase/genetics*; Rad51 Recombinase/metabolism; Recombination, Genetic*; Replication Protein A/metabolism

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