|Title:||Smarcal1 promotes double-strand-break repair by nonhomologous end-joining.|
|Authors:||Keka, Islam Shamima|
Rahman, Md Maminur
|Author's alias:||本間, 正充|
|Publisher:||Oxford University Press|
|Journal title:||Nucleic acids research|
|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.|
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|Appears in Collections:||Journal Articles |
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