BRCA2 Is Required for Homology-Directed Repair of Chromosomal Breaks

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 th...

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Bibliographic Details
Published in:Molecular cell 2001-02, Vol.7 (2), p.263-272
Main Authors: Moynahan, Mary Ellen, Pierce, Andrew J, Jasin, Maria
Format: Article
Language:English
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
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Summary: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.
ISSN:1097-2765
1097-4164
DOI:10.1016/S1097-2765(01)00174-5