title: Common nonsense mutations in RAD52.
abstract: RAD51, RAD52, and RAD54 encode proteins that are critical to the repair of double-strand DNA breaks by homologous recombination. The physical interactions among the products of RAD51, BRCA1, and BRCA2 have suggested that the BRCA1 and BRCA2 breast cancer susceptibility genes may function, at least in part, in this DNA damage repair pathway. Given the observation that different genes within a common functional pathway may be targeted by mutations in human cancers, we analyzed RAD51, RAD52, and RAD54 for the presence of germ-line mutations in 100 cases with early-onset breast cancer and for somatic mutations in 15 human breast cancer cell lines. Two premature stop codons, Ser346ter and Tyr415ter, were identified in germ-line RAD52 alleles from 5% of early-onset breast cancer cases. Together, these two heterozygous mutations were also found in 8% of a healthy control population, indicating that they do not confer an increased risk for breast cancer. A rare germ-line missense mutation was identified in RAD54, whereas no sequence variants were found in RAD51. None of the three RAD genes demonstrated somatic mutations in breast cancer cell lines. We conclude that, despite their potential functional association with the BRCA gene products, RAD51, RAD52, and RAD54 are not themselves targeted by mutations in human breast cancer. The presence of common nonsense mutations in RAD52 within the population may have significance for other conditions associated with potential alterations in DNA damage repair pathways.
authors.affiliation: Center for Cancer Risk Analysis, Massachusetts General Hospital Cancer Center, and Harvard Medical School, Charlestown 02129, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Bell
authors.forename: D C
authors.initials: DC
authors.lastname: Wahrer
authors.forename: D H
authors.initials: DH
authors.lastname: Kang
authors.forename: M S
authors.initials: MS
authors.lastname: MacMahon
authors.forename: M G
authors.initials: MG
authors.lastname: FitzGerald
authors.forename: C
authors.initials: C
authors.lastname: Ishioka
authors.forename: K J
authors.initials: KJ
authors.lastname: Isselbacher
authors.forename: M
authors.initials: M
authors.lastname: Krainer
authors.forename: D A
authors.initials: DA
authors.lastname: Haber
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D004265:DNA Helicases; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D009154:Mutation; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes