Homologous recombinational repair of DNA ensures mammalian chromosome stability.
The process of homologous recombinational repair (HRR) is a major DNA repair pathway that acts on double-strand breaks and interstrand crosslinks, and probably to a lesser extent on other kinds of DNA damage. HRR provides a mechanism for the error-free removal of damage present in DNA that has replicated (S and G2 phases). Thus, HRR acts in a critical way, in coordination with the S and G2 checkpoint machinery, to eliminate chromosomal breaks before the cell division occurs. Many of the human HRR genes, including five Rad51 paralogs, have been identified, and knockout mutants for most of these genes are available in chicken DT40 cells. In the mouse, most of the knockout mutations cause embryonic lethality. The Brca1 and Brca2 breast cancer susceptibility genes appear to be intimately involved in HRR, but the mechanistic basis is unknown. Biochemical studies with purified proteins and cell extracts, combined with cytological studies of nuclear foci, have begun to establish an outline of the steps in mammalian HRR. This pathway is subject to complex regulatory controls from the checkpoint machinery and other processes, and there is increasing evidence that loss of HRR gene function can contribute to tumor development. This review article is meant to be an update of our previous review [Biochimie 81 (1999) 87].
Thompson
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Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, L-441, P.O. Box 808, Livermore, CA 94551-0808, USA. thompson14@llnl.gov
Schild
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D000818:Animals; D030161:Avian Proteins; D002875:Chromosomes; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D008322:Mammals; D009369:Neoplasms / Q000235:genetics; D051135:Rad51 Recombinase; D011995:Recombination, Genetic
D030161:Avian Proteins; D004268:DNA-Binding Proteins; C495150:RAD51 protein, Gallus gallus; C495153:RAD51 protein, human; D051135:Rad51 Recombinase