Downloads: 207

Files in This Item:
File Description SizeFormat 
nar_gkv621.pdf850.69 kBAdobe PDFView/Open
Title: Smarcal1 promotes double-strand-break repair by nonhomologous end-joining.
Authors: Keka, Islam Shamima
Maede, Yuko
Rahman, Md Maminur
Sakuma, Tetsushi
Honma, Masamitsu
Yamamoto, Takashi
Takeda, Shunichi
Sasanuma, Hiroyuki  kyouindb  KAKEN_id
Author's alias: 本間, 正充
山本, 卓
武田, 俊一
笹沼, 博之
Issue Date: 18-Jun-2015
Publisher: Oxford University Press
Journal title: Nucleic acids research
Volume: 43
Issue: 13
End page: 6359
Thesis number: 6372
Abstract: Smarcal1 is a SWI/SNF-family protein with an ATPase domain involved in DNA-annealing activities and a binding site for the RPA single-strand-DNA-binding protein. Although the role played by Smarcal1 in the maintenance of replication forks has been established, it remains unknown whether Smarcal1 contributes to genomic DNA maintenance outside of the S phase. We disrupted the SMARCAL1 gene in both the chicken DT40 and the human TK6 B cell lines. The resulting SMARCAL1(-/-) clones exhibited sensitivity to chemotherapeutic topoisomerase 2 inhibitors, just as nonhomologous end-joining (NHEJ) null-deficient cells do. SMARCAL1(-/-) cells also exhibited an increase in radiosensitivity in the G1 phase. Moreover, the loss of Smarcal1 in NHEJ null-deficient cells does not further increase their radiosensitivity. These results demonstrate that Smarcal1 is required for efficient NHEJ-mediated DSB repair. Both inactivation of the ATPase domain and deletion of the RPA-binding site cause the same phenotype as does null-mutation of Smarcal1, suggesting that Smarcal1 enhances NHEJ, presumably by interacting with RPA at unwound single-strand sequences and then facilitating annealing at DSB ends. SMARCAL1(-/-)cells showed a poor accumulation of Ku70/DNA-PKcs and XRCC4 at DNA-damage sites. We propose that Smarcal1 maintains the duplex status of DSBs to ensure proper recruitment of NHEJ factors to DSB sites.
Description: シムケ免疫不全・骨形成不全症の原因遺伝子SMARCAL1は、DNA二重鎖切断損傷からゲノムを守る. 京都大学プレスリリース. 2015-06-23.
Rights: © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI(Published Version): 10.1093/nar/gkv621
PubMed ID: 26089390
Related Link:
Appears in Collections:Journal Articles

Show full item record

Export to RefWorks

Export Format: 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.