Open AccessThe breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA
Author(s) -
Tina Thorslund,
Michael J. McIlwraith,
Sarah A. Compton,
Sergey Lekomtsev,
Mark Petronczki,
Jack D. Griffith,
Stephen C. West
Publication year - 2010
Publication title -
nature structural and molecular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.448
H-Index - 270
eISSN - 1545-9993
pISSN - 1545-9985
DOI - 10.1038/nsmb.1905
Subject(s) - rad51 , recombinase , dna , brca2 protein , replication protein a , biology , genome instability , homologous recombination , dna replication , microbiology and biotechnology , cancer research , dna binding protein , genetics , dna damage , chemistry , mutation , gene , transcription factor , recombination , germline mutation
Individuals with BRCA2 mutations are predisposed to breast cancers owing to genome instability. To determine the functions of BRCA2, the human protein was purified. It was found to bind selectively to single-stranded DNA (ssDNA), and to ssDNA in tailed duplexes and replication fork structures. Monomeric and dimeric forms of BRCA2 were observed by EM. BRCA2 directed the binding of RAD51 recombinase to ssDNA, reduced the binding of RAD51 to duplex DNA and stimulated RAD51-mediated DNA strand exchange. These observations provide a molecular basis for the role of BRCA2 in the maintenance of genome stability.