title: The consequences of Rad51 overexpression for normal and tumor cells.
abstract: The Rad51 recombinase is an essential factor for homologous recombination and the repair of DNA double strand breaks, binding transiently to both single stranded and double stranded DNA during the recombination reaction. The use of a homologous recombination mechanism to repair DNA damage is controlled at several levels, including the binding of Rad51 to single stranded DNA to form the Rad51 nucleofilament, which is controlled through the action of DNA helicases that can counteract nucleofilament formation. Overexpression of Rad51 in different organisms and cell types has a wide assortment of consequences, ranging from increased homologous recombination and increased resistance to DNA damaging agents to disruption of the cell cycle and apoptotic cell death. Rad51 expression is increased in p53-negative cells, and since p53 is often mutated in tumor cells, there is a tendency for Rad51 to be overexpressed in tumor cells, leading to increased resistance to DNA damage and drugs used in chemotherapies. As cells with increased Rad51 levels are more resistant to DNA damage, there is a selection for tumor cells to have higher Rad51 levels. While increased Rad51 can provide drug resistance, it also leads to increased genomic instability and may contribute to carcinogenesis.
authors.affiliation: Department of Biochemistry, New York University School of Medicine, NYU Medical Center, 550 First Avenue, New York, NY 10016, United States. hannah.klein@med.nyu.edu
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Klein
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D051135:Rad51 Recombinase / Q000235:genetics* / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics
chemical_list: D051135:Rad51 Recombinase