Double-strand-break-induced homologous recombination in mammalian cells.
In mammalian cells, the repair of DNA double-strand breaks (DSBs) occurs by both homologous and non-homologous mechanisms. Indirect evidence, including that from gene targeting and random integration experiments, had suggested that non-homologous mechanisms were significantly more frequent than homologous ones. However, more recent experiments indicate that homologous recombination is also a prominent DSB repair pathway. These experiments show that mammalian cells use homologous sequences located at multiple positions throughout the genome to repair a DSB. However, template preference appears to be biased, with the sister chromatid being preferred by 2-3 orders of magnitude over a homologous or heterologous chromosome. The outcome of homologous recombination in mammalian cells is predominantly gene conversion that is not associated with crossing-over. The preference for the sister chromatid and the bias against crossing-over seen in mitotic mammalian cells may have developed in order to reduce the potential for genome alterations that could occur when other homologous repair templates are utilized. In attempts to understand further the mechanism of homologous recombination, the proteins that promote this process are beginning to be identified. To date, four mammalian proteins have been demonstrated conclusively to be involved in DSB repair by homologous recombination: Rad54, XRCC2, XRCC3 and BRCA1. This paper summarizes results from a number of recent studies.
Johnson
R D
RD
Cell Biology Program, Memorial Sloan-Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, 1275 York Avenue, New York, NY 10021, U.S.A.
Jasin
M
M
D000818:Animals; D001483:Base Sequence; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005785:Gene Conversion / Q000235:genetics; D008322:Mammals / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017385:Sequence Homology; D012854:Sister Chromatid Exchange / Q000235:genetics
D029701:Saccharomyces cerevisiae Proteins; C037725:SCEI protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific