DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells

被引:94
作者
Gudmundsdottir, K
Lord, CJ
Witt, E
Tutt, ANJ
Ashworth, A
机构
[1] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England
[2] Guys Hosp, London SE1 9RT, England
关键词
DSS1; homologous recombination; breast cancer susceptibility; BRCA2; RAD51; DNA damage;
D O I
10.1038/sj.embor.7400255
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:989 / 993
页数:5
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