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Homologous Recombination, but Not DNA Repair, is Reduced in Vertebrate Cells Deficient in RAD52

Overview
Journal Mol Cell Biol
Specialty Cell Biology
Date 1998 Oct 17
PMID 9774659
Citations 101
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Abstract

Rad52 plays a pivotal role in double-strand break (DSB) repair and genetic recombination in Saccharomyces cerevisiae, where mutation of this gene leads to extreme X-ray sensitivity and defective recombination. Yeast Rad51 and Rad52 interact, as do their human homologues, which stimulates Rad51-mediated DNA strand exchange in vitro, suggesting that Rad51 and Rad52 act cooperatively. To define the role of Rad52 in vertebrates, we generated RAD52(-/-) mutants of the chicken B-cell line DT40. Surprisingly, RAD52(-/-) cells were not hypersensitive to DNA damages induced by gamma-irradiation, methyl methanesulfonate, or cis-platinum(II)diammine dichloride (cisplatin). Intrachromosomal recombination, measured by immunoglobulin gene conversion, and radiation-induced Rad51 nuclear focus formation, which is a putative intermediate step during recombinational repair, occurred as frequently in RAD52(-/-) cells as in wild-type cells. Targeted integration frequencies, however, were consistently reduced in RAD52(-/-) cells, showing a clear role for Rad52 in genetic recombination. These findings reveal striking differences between S. cerevisiae and vertebrates in the functions of RAD51 and RAD52.

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References
1.
Muris D, Vreeken K, Schmidt H, Ostermann K, Clever B, Lohman P . Homologous recombination in the fission yeast Schizosaccharomyces pombe: different requirements for the rhp51+, rhp54+ and rad22+ genes. Curr Genet. 1997; 31(3):248-54. DOI: 10.1007/s002940050202. View

2.
Sugawara N, Ivanov E, RAY B, Wu X, Haber J . DNA structure-dependent requirements for yeast RAD genes in gene conversion. Nature. 1995; 373(6509):84-6. DOI: 10.1038/373084a0. View

3.
Hannan M, Zimmer S, Hazle J . Mechanisms of cisplatin (cis-diamminodichloroplatinum II)-induced cytotoxicity and genotoxicity in yeast. Mutat Res. 1984; 127(1):23-30. DOI: 10.1016/0027-5107(84)90136-2. View

4.
Tashiro S, Kotomura N, Shinohara A, Tanaka K, Ueda K, Kamada N . S phase specific formation of the human Rad51 protein nuclear foci in lymphocytes. Oncogene. 1996; 12(10):2165-70. View

5.
Buerstedde J, REYNAUD C, Humphries E, Olson W, Ewert D, Weill J . Light chain gene conversion continues at high rate in an ALV-induced cell line. EMBO J. 1990; 9(3):921-7. PMC: 551754. DOI: 10.1002/j.1460-2075.1990.tb08190.x. View