WASH interacts with Ku to regulate DNA double-stranded break repair

iScience

Jie Ge¹  Daniel D. Billadeau²  Xiao-Hui Du³  He Sun³  Tao Wang³  Yu Hong³  Li Fan³  Xian Hong³  Jian-Wen Zhou³  Zhi-Hui Deng³ 

[1] Department of Epidemiology and Statistics, School of Public Health, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China;Division of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA;Laboratory of Protein Structure and Function, Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China;

关键词: Biological sciences;    Molecular biology;    Cell biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH), an actin nucleation-promoting factor, is present in the nucleus where it regulates gene transcription and maintains nuclear organization. Here, we show that WASH interacts with core non-homologous end-joining (NHEJ) factors including Ku70/Ku80 and DNA-PKcs, and Ku70/Ku80 is involved in the recruitment of WASH to the sites of DNA double-stranded break (DSB). WASH depletion leads to increased cell sensitivity and impaired DNA repair capacity in response to etoposide-induced DSBs and reduces NHEJ efficiency. Mechanistically, we show that loss of WASH inhibits the phosphorylation of DNA-PKcs, H2AX, and KAP1 after DSB induction and reduces chromatin relaxation and the recruitment of several downstream NHEJ factors to DSBs. Moreover, WASH role in DSB repair depends on its conserved C-terminal VCA domain and Arp2/3 activation. Our findings reveal a function and mechanistic insight for WASH in DNA DSB repair by the NHEJ pathway.

【 授权许可】

Unknown