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

Tao Wang, Xiao Hui Du, Yu Hong, Xian Hong, Li Fan, Jian Wen Zhou, He Sun, Jie Ge, Daniel D. Billadeau, Zhi Hui Deng

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number103676
Issue number1
StatePublished - Jan 21 2022


  • Biological sciences
  • Cell biology
  • Molecular biology

ASJC Scopus subject areas

  • General


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