ELL2 regulates DNA non-homologous end joining (NHEJ) repair in prostate cancer cells

ELL2 is an androgen-responsive gene that is expressed by prostate epithelial cells and is frequently down-regulated in prostate cancer. Deletion of Ell2 in the murine prostate induced murine prostatic intraepithelial neoplasia and ELL2 knockdown enhanced proliferation and migration in C4-2 prostate cancer cells. Here, knockdown of ELL2 sensitized prostate cancer cells to DNA damage and over expression of ELL2 protected prostate cancer cells from DNA damage. Knockdown of ELL2 impaired non homologous end joining repair but not homologous recombination repair. Transfected ELL2 co-immunoprecipitated with both Ku70 and Ku80 proteins. ELL2 could bind to and co-accumulate with Ku70/Ku80 proteins at sites of DNA damage. Knockdown of ELL2 dramatically inhibited Ku70 and Ku80 recruitment and retention at DNA double-strand break sites in prostate cancer cells. The impaired recruitment of Ku70 and Ku80 proteins to DNA damage sites upon ELL2 knockdown was rescued by re-expression of an ELL2 transgene insensitive to siELL2. This study suggests that ELL2 is required for efficient NHEJ repair via Ku70/Ku80 in prostate cancer cells. (C) 2017 Elsevier B.V. All rights reserved.