title: Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability.
abstract: Genomic instability is characteristic of tumor cells, and a strong correlation exists between abnormal karyotype and tumorigenicity. Increased expression of the homologous recombination and DNA repair protein Rad51 has been reported in immortalized and tumor cells, which could alter recombination pathways to contribute to the chromosomal rearrangements found in these cells. We used a genetic system to examine the potential for multiple double-strand breaks to lead to genome rearrangements in the presence of increased Rad51 expression. Analysis of repair revealed a novel class of products consistent with crossing over, involving gene conversion associated with an exchange of flanking markers leading to chromosomal translocations. Increased Rad51 also promoted aneuploidy and multiple chromosomal rearrangements. These data provide a link between elevated Rad51 protein levels, genome instability, and tumor progression.
authors.affiliation: Department of Pathology, Institute of Cancer Genetics, Columbia University College of Physicians and Surgeons, 1150 St Nicholas Avenue, New York, NY 10032, USA. car10@columbia.edu
authors.forename: Christine
authors.initials: C
authors.lastname: Richardson
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Stark
authors.forename: Melissa
authors.initials: M
authors.lastname: Ommundsen
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
mesh_terms: D000782:Aneuploidy; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D042822:Genomic Instability; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D051135:Rad51 Recombinase; D011995:Recombination, Genetic / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase