1. Academic Validation
  2. WASH interacts with Ku to regulate DNA double-stranded break repair

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

  • iScience. 2021 Dec 25;25(1):103676. doi: 10.1016/j.isci.2021.103676.
Tao Wang 1 Xiao-Hui Du 1 Yu Hong 1 Xian Hong 1 Li Fan 1 Jian-Wen Zhou 1 He Sun 1 Jie Ge 2 Daniel D Billadeau 3 Zhi-Hui Deng 1
Affiliations

Affiliations

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

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.

Keywords

Biological sciences; Cell biology; Molecular biology.

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