title: Similar effects of Brca2 truncation and Rad51 paralog deficiency on immunoglobulin V gene diversification in DT40 cells support an early role for Rad51 paralogs in homologous recombination.
abstract: BRCA2 is a tumor suppressor gene that is linked to hereditary breast and ovarian cancer. Although the Brca2 protein participates in homologous DNA recombination (HR), its precise role remains unclear. From chicken DT40 cells, we generated BRCA2 gene-deficient cells which harbor a truncation at the 3' end of the BRC3 repeat (brca2tr). Comparison of the characteristics of brca2tr cells with those of other HR-deficient DT40 clones revealed marked similarities with rad51 paralog mutants (rad51b, rad51c, rad51d, xrcc2, or xrcc3 cells). The phenotypic similarities include a shift from HR-mediated diversification to single-nucleotide substitutions in the immunoglobulin variable gene segment and the partial reversion of this shift by overexpression of Rad51. Although recent evidence supports at least Xrcc3 and Rad51C playing a role late in HR, our data suggest that Brca2 and the Rad51 paralogs may also contribute to HR at the same early step, with their loss resulting in the stimulation of an alternative, error-prone repair pathway.
authors.affiliation: Department of Radiation Genetics, Faculty of Medicine, Kyoto University, Konoe Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hatanaka
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yamazoe
authors.forename: Julian E
authors.initials: JE
authors.lastname: Sale
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Sonoda
authors.forename: Koji
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yonetani
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D030161:Avian Proteins; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005785:Gene Conversion / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D009154:Mutation / Q000235:genetics*; D051135:Rad51 Recombinase; D011995:Recombination, Genetic / Q000235:genetics*
chemical_list: D030161:Avian Proteins; D024682:BRCA2 Protein; D004268:DNA-Binding Proteins; D007135:Immunoglobulin Variable Region; C495150:RAD51 protein, Gallus gallus; D051135:Rad51 Recombinase