ELL2 regulates DNA non-homologous end joining (NHEJ) repair in prostate cancer cells. (28th February 2018)

• Record Type: Journal Article
• Authors: Zang, Yachen; Pascal, Laura E.; Zhou, Yibin; Qiu, Xiaonan; Wei, Leizhen; Ai, Junkui; Nelson, Joel B.; Zhong, Mingming; Xue, Boxin; Wang, Shaoxiong; Yang, Dongrong; Lan, Li; Shan, Yuxi; Wang, Zhou
• Is Part Of: Cancer letters. Volume 415(2018)
• Page Start: 198
• Page End: 207
• Publication Date: 2018-02-28
• Subjects: ELL2 -- Prostate cancer -- DNA damage repair -- Non-homologous end joining -- Ku70 -- Ku80; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.11.028
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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 overexpression 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. Highlights: ELL2 knockdown sensitized prostate cancer cells to DNA damage; ELL2 overexpression protected cells. ELL2 knockdown impaired non-homologous end joining repair but not homologous recombination repair. ELL2 could bind to and co-accumulate with Ku70/Ku80 proteins at DNA damage sites. ELL2 knockdown inhibited Ku70/Ku80 recruitment and retention at DNA double-strand break sites. ELL2 is required for efficient NHEJ repair via Ku70/Ku80 in prostate cancer cells.