Recombination mediator and Rad51 targeting activities of a human BRCA2 polypeptide.
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.
Mesh Terms:
BRCA2 Protein, DNA Damage, DNA Primers, DNA Repair, DNA, Single-Stranded, Humans, Peptide Fragments, Rad51 Recombinase, Recombination, Genetic, Replication Protein A
BRCA2 Protein, DNA Damage, DNA Primers, DNA Repair, DNA, Single-Stranded, Humans, Peptide Fragments, Rad51 Recombinase, Recombination, Genetic, Replication Protein A
J. Biol. Chem.
Date: Apr. 28, 2006
PubMed ID: 16513631
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