BRCA2 is required for homology-directed repair of chromosomal breaks Journal Article

  


Authors: Moynahan, M. E.; Pierce, A. J.; Jasin, M.
Article Title: BRCA2 is required for homology-directed repair of chromosomal breaks
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.
Keywords: controlled study; gene mutation; human cell; dna-binding proteins; exons; sequence deletion; nonhuman; animal cell; mouse; animals; mice; dna damage; gene targeting; dna repair; neoplasm proteins; cell line; protein binding; gene locus; tumor cells, cultured; transfection; brca1 protein; brca2 protein; carcinogenesis; animalia; transcription factors; genetic recombination; recombination, genetic; stem cells; chromosome breakage; genes, reporter; sequence homology; sequence homology, nucleic acid; endonuclease; rad51 recombinase; blotting, southern; precipitin tests; humans; human; article
Journal Title: Molecular Cell
Volume: 7
Issue: 2
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2001-02-01
Start Page: 263
End Page: 272
Language: English
DOI: 10.1016/s1097-2765(01)00174-5
PUBMED: 11239455
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0035099044&partnerID=40&md5=fe5eca941c13c501ee28c73a8b1aa7e5
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Mary Ellen Moynahan
    105 Moynahan
  2. Andrew J Pierce
    11 Pierce
  3. Maria Jasin
    251 Jasin
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