Effects of SWI/SNF complex on DNA damage repair in heterochromatin of embryonic fibroblast cells  

作　　者：Hong Zhang Yinyin Shu Mintao Ji 

机构地区：[1]Obstetrics and Gynecology Department,First Affiliated Hospital of Soochow University,Suzhou 215006,China [2]State Key Laboratory of Radiation Medicine and Protection,School of Radiation Medicine and Protection,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions,Medical College of Soochow University,Suzhou 215123,China

出　　处：《Radiation Medicine and Protection》2023年第4期214-220,共7页放射医学与防护（英文）

基　　金：supported by grants from National Natural Science Foundation of China(31971165 and 82173465);Leading Talents Program of Gusu District(ZXL2022454);Jiangsu Provincial Outstanding Postdoctoral Program(2023ZB254),China.

摘　　要：Objective:To investigate the impact of SWI/SNF complex on heterochromatin DNA damage repair after exposure to X-ray irradiation,in order to explore the underlying mechanism.Methods:NIH3T3 and MRC5 cells were treated with 50 nmol/L siRNA targeting SWI/SNF complex subunits(BRM,ARID1A,BRG1 and SNF5),and YAP/TAZ.At 24 h after transfection,the cells were irradiated with 0.5 and 1 Gy of X-rays.At 20,60 and 240 min post-irradiation,γH2AX assay was performed to evaluate the radiation response in total or heterochromatin.Comet assay was used to determine the role of YAP/TAZ in DNA damage when the cells were irradiated with 4 Gy of X-rays.NIH3T3 were treated with 50 nmol/L siRNA targeting BRM/BRG1 and YAP/TAZ to determine their relationship on heterochromatin DNA damage repair.Results:In NIH3T3,SWI/SNF complex subunits(BRM,ARID1A and BRG1)knock-down increasedγH2AX in total and heterochromatin at 1 Gy 60 min post-irradiation(P<0.05),while SNF5 knock-down decreased heterochromatinγH2AX at 1 Gy 20 min post-irradiation(P<0.05).In MRC5,BRM and BRG1 knock-down increasedγH2AX in total and heterochromatin at 1 Gy 60 min post-irradiation(P<0.05).Inconsistently,ARID1A knockdown did not affect it,and SNF5 knock-down increased heterochromatinγH2AX at 1 Gy 60 min post-irradiation(P<0.05).Moreover,YAP/TAZ knock-down decreased heterochromatinγH2AX in NIH3T3 and MRC5(P<0.05).Meanwhile,YAP/TAZ knock-down decreased Tail Moment in comet assay at 4 Gy 60 min post-irradiation(P<0.05).BRM/BRG1 combining with YAP/TAZ knock-down significantly decreased heterochromatinγH2AX compared with single BRM/BRG1 knock-down at 0.5 Gy 60 min post-irradiation(P<0.05).Conclusions:The SWI/SNF complex subunits exhibited varying effects on DNA damage repair.BRM/BRG1 knockdown promotedγH2AX accumulation in heterochromatin through YAP/TAZ.This study provides a novel direction for DNA damage repair and sheds light on the role of SWI/SNF complex in response to DNA damage repair in heterochromatin.

关 键 词：SWI/SNF complex BRM/BRG1 HETEROCHROMATIN DNA damage repair YAP/TAZ 

分 类 号：R81[医药卫生—放射医学]