Rad51‐deficient vertebrate cells accumulate chromosomal breaks prior to cell death

Rad51‐deficient vertebrate cells accumulate chromosomal breaks prior to cell death Yeast rad51 mutants are viable, but extremely sensitive to γ‐rays due to defective repair of double‐strand breaks. In contrast, disruption of the murine RAD51 homologue is lethal, indicating an essential role of Rad51 in vertebrate cells. We generated clones of the chicken B lymphocyte line DT40 carrying a human RAD51 transgene under the control of a repressible promoter and subsequently disrupted the endogenous RAD51 loci. Upon inhibition of the RAD51 transgene, Rad51− cells accumulated in the G2/M phase of the cell cycle before dying. Chromosome analysis revealed that most metaphase‐arrested Rad51− cells carried isochromatid‐type breaks. In conclusion, Rad51 fulfils an essential role in the repair of spontaneously occurring chromosome breaks in proliferating cells of higher eukaryotes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

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Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/17.2.598
Publisher site
See Article on Publisher Site

Abstract

Yeast rad51 mutants are viable, but extremely sensitive to γ‐rays due to defective repair of double‐strand breaks. In contrast, disruption of the murine RAD51 homologue is lethal, indicating an essential role of Rad51 in vertebrate cells. We generated clones of the chicken B lymphocyte line DT40 carrying a human RAD51 transgene under the control of a repressible promoter and subsequently disrupted the endogenous RAD51 loci. Upon inhibition of the RAD51 transgene, Rad51− cells accumulated in the G2/M phase of the cell cycle before dying. Chromosome analysis revealed that most metaphase‐arrested Rad51− cells carried isochromatid‐type breaks. In conclusion, Rad51 fulfils an essential role in the repair of spontaneously occurring chromosome breaks in proliferating cells of higher eukaryotes.

Journal

The EMBO JournalWiley

Published: Mar 15, 1999

Keywords: ; ; ;

References

  • Constant and variable features of avian chromosomes
    Bloom, SE; Delany, ME; Muscarella, DE
  • Light chain gene conversion continues at high rate in an ALV‐induced cell line
    Buerstedde, JM; Reynaud, CA; Humphries, EH; Olson, W; Ewert, DL; Weill, JC
  • A super new twist on the initiation of meiotic recombination
    Haber, JE
  • The molecular and cellular biology of the yeast Saccharomyces
    Petes, TD; Malone, RE; Symington, LS
  • Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2
    Sharan, SK

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