title: DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells.
abstract: BRCA2 is a breast cancer susceptibility gene implicated in the repair of double-strand breaks by homologous recombination with RAD51. BRCA2 associates with a 70-amino-acid protein, DSS1, but the functional significance of this interaction has remained unclear. Recently, deficiency of a DSS1 orthologue in the fungus Ustilago maydis has been shown to cause a defect in recombinational DNA repair. Here we have investigated the consequences of DSS1 depletion in mammalian cells. We show that like BRCA2, DSS1 is required for DNA damage-induced RAD51 focus formation and for the maintenance of genomic stability, indicating a function conserved from lower eukaryotes to humans. However, DSS1 seems to be not required for BRCA2 or RAD51 stability or for BRCA2 and RAD51 to interact, raising the possibility that DSS1 may be required for the BRCA2-RAD51 complex to become associated with sites of DNA damage.
authors.affiliation: The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Katrin
authors.initials: K
authors.lastname: Gudmundsdottir
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lord
authors.forename: Emily
authors.initials: E
authors.lastname: Witt
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: Tutt
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000378:metabolism; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*; D051135:Rad51 Recombinase
chemical_list: D024682:BRCA2 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; C484606:SEM1 protein, human; C108199:Shfdg1 protein, mouse; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse; D046988:Proteasome Endopeptidase Complex