@article{05dad8c406cc4ba39716ad7a9e536e1e,
title = "WASH interacts with Ku to regulate DNA double-stranded break repair",
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",
author = "Tao Wang and Du, {Xiao Hui} and Yu Hong and Xian Hong and Li Fan and Zhou, {Jian Wen} and He Sun and Jie Ge and Billadeau, {Daniel D.} and Deng, {Zhi Hui}",
note = "Funding Information: We thank Dr. Hua-Dong Pei (The George Washington University, DC, USA) for EJ5-GFP, DR-GFP, and pCBASceI plasmids. This work was supported by grants from The National Natural Science Foundation of China ( 3180064 8 to T.W., 31640017 and 32071409 to Z.-H.D.), the Education Department Foundation of Heilongjiang Province ( 2020-KYYWF-0001 to T.W., 2018-KYYWF-0100 to X.-H.D.), the Postdoctoral Scientific Research Developmental Fund of Heilongjiang ( LBH-Q15144 to Z.-H.D.), the International Cooperation Program of Qiqihar Medical University ( QMSI2017GJ-01 to Z.-H.D.). Funding Information: We thank Dr. Hua-Dong Pei (The George Washington University, DC, USA) for EJ5-GFP, DR-GFP, and pCBASceI plasmids. This work was supported by grants from The National Natural Science Foundation of China (31800648 to T.W. 31640017 and 32071409 to Z.-H.D.), the Education Department Foundation of Heilongjiang Province (2020-KYYWF-0001 to T.W. 2018-KYYWF-0100 to X.-H.D.), the Postdoctoral Scientific Research Developmental Fund of Heilongjiang (LBH-Q15144 to Z.-H.D.), the International Cooperation Program of Qiqihar Medical University (QMSI2017GJ-01 to Z.-H.D.). Conceptualization, T.W. and Z.-H.D.; investigation, T.W. X.-H.D. Y.H. and X.H. performed the major experiments with assistance from L.F. J.-W.Z. H.S. and J.G.; writing ? original draft, T.W. and Z.-H.D.; writing ? review and editing, Z.-H.D. and D.D.B.; funding acquisition, T.W. and Z.-H.D.; supervision, Z.-H.D. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2022",
month = jan,
day = "21",
doi = "10.1016/j.isci.2021.103676",
language = "English (US)",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "1",
}