DSS1 is required for the stability of BRCA2

J. Li, C. Zou, Y. Bai, D. E. Wazer, V. Band, Q. Gao

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


DSS1 is an evolutionarily conserved acidic protein that binds to BRCA2. However, study of the function of DSS1 in mammalian cells has been hampered because endogen-ous DSS1 has not been detectable by Western blotting. Here, we developed a modified Western blotting protocol that detects endogenous DSS1 protein, and used it to study the function of DSS1 and its interaction with BRCA2 in mammalian cells. We found that essentially all BRCA2 in human cell lines is associated with DSS1. Importantly, we found that RNAi knockdown of DSS1 in human cell lines led to dramatic loss of BRCA2 protein, mainly due to its increased degradation. Furthermore, the stability of BRCA2 mutant devoid of the DSS1-binding domain is unaffected by the depletion of DSS1. Most notably, like BRCA2 depletion, DSS1 depletion also led to hypersensitivity to DNA damage. These results demonstrated that the stability of BRCA2 protein in mammalian cells depends on the presence of DSS1. Deletion or mutation of DSS1 or suppression of its expression by other mechanisms are therefore potential causative mechanisms for human breast and ovarian cancer. Such mechanisms may be relevant to sporadic as well as familiar breast cancer where BRCA1 and BRCA2 mutations are not present.

Original languageEnglish (US)
Pages (from-to)1186-1194
Number of pages9
Issue number8
StatePublished - Feb 23 2006
Externally publishedYes


  • BRCA2
  • Breast cancer
  • DNA damage repair
  • DSS1
  • Protein degradation
  • Suppressor gene
  • Tumor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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