Downregulation of the cancer susceptibility protein WRAP53β in epithelial ovarian cancer leads to defective DNA repair and poor clinical outcome.

ABSTRACT: Alterations in the scaffold protein WRAP53β have previously been linked to carcinogenesis and, in particular, associated with an increased risk for epithelial ovarian cancer. Here, we investigated the pathogenic impact and prognostic significance of WRAP53β in connection with epithelial ovarian cancer and examined the underlying mechanisms. We find that reduced expression of WRAP53β in ovarian tumors correlated with attenuated DNA damage response and poor patient survival. Furthermore, in ovarian cancer cell lines, WRAP53β was rapidly recruited to DNA double-strand breaks, where it orchestrated the recruitment of repair factors involved in homologous recombination and non-homologous end joining, including RNF168, 53BP1, BRCA1 and RAD51. Mechanistically, WRAP53β accomplishes this by facilit

SUBMITTER: Hedstrom E 

PROVIDER: S-EPMC4632285 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature