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BRCA2 is required for homology-directed repair of chromosomal breaks.
- Source :
-
Molecular cell [Mol Cell] 2001 Feb; Vol. 7 (2), pp. 263-72. - Publication Year :
- 2001
-
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.
- Subjects :
- Animals
BRCA2 Protein
Blotting, Southern
DNA Damage genetics
DNA-Binding Proteins metabolism
Exons genetics
Gene Targeting
Genes, Reporter
Humans
Mice
Neoplasm Proteins genetics
Precipitin Tests
Protein Binding
Rad51 Recombinase
Sequence Deletion genetics
Stem Cells
Transcription Factors genetics
Transfection
Tumor Cells, Cultured
Chromosome Breakage genetics
DNA Repair genetics
Neoplasm Proteins metabolism
Recombination, Genetic
Sequence Homology, Nucleic Acid
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-2765
- Volume :
- 7
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 11239455
- Full Text :
- https://doi.org/10.1016/s1097-2765(01)00174-5