BRCA2 is required for homology-directed repair of chromosomal breaks - PubMed

BRCA2 is required for homology-directed repair of chromosomal breaks

M E Moynahan et al. Mol Cell. 2001 Feb.

Free article

Abstract

The BRCA2 tumor suppressor has been implicated in the maintenance of chromosomal stability through a function in DNA repair. In this report, we examine human and mouse cell lines containing different BRCA2 mutations for their ability to repair chromosomal breaks by homologous recombination. Using the I-SceI endonuclease to introduce a double-strand break at a specific chromosomal locus, we find that BRCA2 mutant cell lines are recombination deficient, such that homology-directed repair is reduced 6- to >100-fold, depending on the cell line. Thus, BRCA2 is essential for efficient homology-directed repair, presumably in conjunction with the Rad51 recombinase. We propose that impaired homology-directed repair caused by BRCA2 deficiency leads to chromosomal instability and, possibly, tumorigenesis, through lack of repair or misrepair of DNA damage.

Comment in

• BRCA2 keeps Rad51 in line. High-fidelity homologous recombination prevents breast and ovarian cancer?

  Powell SN, Willers H, Xia F. Powell SN, et al. Mol Cell. 2002 Dec;10(6):1262-3. doi: 10.1016/s1097-2765(02)00789-x. Mol Cell. 2002. PMID: 12504001

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