BRCA2 Is Required for Homology-Directed Repair of Chromosomal Breaks

• Published in: Molecular cell Vol. 7; no. 2; pp. 263 - 272
• Main Authors: Moynahan, Mary Ellen, Pierce, Andrew J, Jasin, Maria
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2001
• Subjects: Animals; Blotting, Southern; BRCA2 gene; BRCA2 Protein; Chromosome Breakage - genetics; DNA Damage - genetics; DNA Repair - genetics; DNA-Binding Proteins - metabolism; Exons - genetics; Gene Targeting; Genes, Reporter; Humans; Mice; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Precipitin Tests; Protein Binding; Rad51 protein; Rad51 Recombinase; Recombination, Genetic; Sequence Deletion - genetics; Sequence Homology, Nucleic Acid; Stem Cells; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Tumor Cells, Cultured
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(01)00174-5

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.