Homologous Repair of DNA Damage and Tumorigenesis: the BRCA Connection
Oncogene (2002) 21, 8981 – 8993 ª 2002 Nature Publishing Group All rights reserved 0950 – 9232/02 $25.00 www.nature.com/onc Homologous repair of DNA damage and tumorigenesis: the BRCA connection Maria Jasin*,1 1Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA Homologous recombination has been recognized in recent Tirkkonen et al., 1997; Turner et al., 2002; Xu et al., years to be an important DNA repair pathway in 1999), are sensitive to DNA damaging agents (Bhatta- mammalian cells, for such damage as chromosomal charyya et al., 2000; Connor et al., 1997; Gowen et al., double-strand breaks. Cells mutated for the genes 1998; Kraakman-van der Zwet et al., 2002; Morimatsu involved in the hereditary breast and ovarian cancer et al., 1998; Moynahan et al., 2001a; Scully et al., 1999; susceptibility syndromes, i.e. BRCA1 and BRCA2, show Sharan et al., 1997; Shen et al., 1998; Zhong et al., defects in DNA repair by homologous recombination, 1999), including ionizing radiation and cross-linking implicating this repair pathway in protecting individuals agents, and have elevated mutation rates (Kraakman- against tumorigenesis. This review summarizes recent van der Zwet et al., 2002; Tutt et al., 2002). During S advances in our understanding of BRCA1 and BRCA2 in phase or upon treatment of cells with DNA damaging DNA repair, as well as insight into these proteins agents or replication inhibitors, both proteins are in gleaned from structure determination of domains of these nuclear foci along with several other proteins involved proteins and the broader evolutionary conservation than in the damage response, including the DNA repair previously appreciated.
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