Depletion of DSS1 protein disables homologous recombinational repair in human cells

作者：Kristensen Colleen N; Bystol Karin M; Li Boran; Serrano Lourdes; Brenneman Mark A^*

来源：Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 2010, 694(1-2): 60-64.

DOI：10.1016/j.mrfmmm.2010.08.007

• DSS1
• BRCA2
• DNA repair
• Homologous recombination
• Proteasomes

DSS1 is a small highly acidic protein widely conserved among eukaryotes as a component of the 195 proteasome and implicated in ubiquitin-mediated proteolysis The BRCA2 tumor suppressor protein functions in homologous recombinational repair (HRR) of DNA double-strand breaks and does so in part through the actions of a carboxy-proximal region that binds DNA and several other proteins including DSS1 In the unicellular eukaryote Ustilago maydis Dss1 interacts with Brh2 a BRCA2-like protein and regulates its function in mediating HRR. We used RNA Interference to deplete DSS1 in human cells and assayed the effects on double-strand break repair by homologous recombination Partial depletion of DSS1 protein in human cells reduced the efficiency of HRR to small fractions of normal levels Residual HRR activity correlated roughly with the residual level of DSS1 expression The results imply that mammalian DSS1 makes a critical contribution to the function of BRCA2 in mediating HRR, and hence to genomic stability Activity of the ubiquitin-proteasome system can influence HRR. However treatment with proteaso

• 出版日期2010-12-10