{"title":"SWI/SNF 复合物对胚胎成纤维细胞异染色质中 DNA 损伤修复的影响","authors":"Hong Zhang , Yinyin Shu , Mintao Ji","doi":"10.1016/j.radmp.2023.10.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>In NIH3T3, SWI/SNF complex subunits (BRM, ARID1A and BRG1) knock-down increased γH2AX in total and heterochromatin at 1 Gy 60 min post-irradiation (<em>P</em> < 0.05), while SNF5 knock-down decreased heterochromatin γH2AX at 1 Gy 20 min post-irradiation (<em>P</em> < 0.05). In MRC5, BRM and BRG1 knock-down increased γH2AX in total and heterochromatin at 1 Gy 60 min post-irradiation (<em>P</em> < 0.05). Inconsistently, ARID1A knock-down did not affect it, and SNF5 knock-down increased heterochromatin γH2AX at 1 Gy 60 min post-irradiation (<em>P</em> < 0.05). Moreover, YAP/TAZ knock-down decreased heterochromatin γH2AX in NIH3T3 and MRC5 (<em>P</em> < 0.05). Meanwhile, YAP/TAZ knock-down decreased Tail Moment in comet assay at 4 Gy 60 min post-irradiation (<em>P</em> < 0.05). BRM/BRG1 combining with YAP/TAZ knock-down significantly decreased heterochromatin γH2AX compared with single BRM/BRG1 knock-down at 0.5 Gy 60 min post-irradiation (<em>P</em> < 0.05).</p></div><div><h3>Conclusions</h3><p>The SWI/SNF complex subunits exhibited varying effects on DNA damage repair. BRM/BRG1 knock-down promoted γH2AX 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.</p></div>","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":"4 4","pages":"Pages 214-220"},"PeriodicalIF":0.0000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666555723000588/pdfft?md5=5e3aa13519a76759b814b68a353c9457&pid=1-s2.0-S2666555723000588-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Effects of SWI/SNF complex on DNA damage repair in heterochromatin of embryonic fibroblast cells\",\"authors\":\"Hong Zhang , Yinyin Shu , Mintao Ji\",\"doi\":\"10.1016/j.radmp.2023.10.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>In NIH3T3, SWI/SNF complex subunits (BRM, ARID1A and BRG1) knock-down increased γH2AX in total and heterochromatin at 1 Gy 60 min post-irradiation (<em>P</em> < 0.05), while SNF5 knock-down decreased heterochromatin γH2AX at 1 Gy 20 min post-irradiation (<em>P</em> < 0.05). In MRC5, BRM and BRG1 knock-down increased γH2AX in total and heterochromatin at 1 Gy 60 min post-irradiation (<em>P</em> < 0.05). Inconsistently, ARID1A knock-down did not affect it, and SNF5 knock-down increased heterochromatin γH2AX at 1 Gy 60 min post-irradiation (<em>P</em> < 0.05). Moreover, YAP/TAZ knock-down decreased heterochromatin γH2AX in NIH3T3 and MRC5 (<em>P</em> < 0.05). Meanwhile, YAP/TAZ knock-down decreased Tail Moment in comet assay at 4 Gy 60 min post-irradiation (<em>P</em> < 0.05). BRM/BRG1 combining with YAP/TAZ knock-down significantly decreased heterochromatin γH2AX compared with single BRM/BRG1 knock-down at 0.5 Gy 60 min post-irradiation (<em>P</em> < 0.05).</p></div><div><h3>Conclusions</h3><p>The SWI/SNF complex subunits exhibited varying effects on DNA damage repair. BRM/BRG1 knock-down promoted γH2AX 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.</p></div>\",\"PeriodicalId\":34051,\"journal\":{\"name\":\"Radiation Medicine and Protection\",\"volume\":\"4 4\",\"pages\":\"Pages 214-220\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2666555723000588/pdfft?md5=5e3aa13519a76759b814b68a353c9457&pid=1-s2.0-S2666555723000588-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Radiation Medicine and Protection\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666555723000588\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Health Professions\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiation Medicine and Protection","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666555723000588","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Health Professions","Score":null,"Total":0}
Effects of SWI/SNF complex on DNA damage repair in heterochromatin of embryonic fibroblast cells
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 increased γH2AX in total and heterochromatin at 1 Gy 60 min post-irradiation (P < 0.05), while SNF5 knock-down decreased heterochromatin γH2AX at 1 Gy 20 min post-irradiation (P < 0.05). In MRC5, BRM and BRG1 knock-down increased γH2AX in total and heterochromatin at 1 Gy 60 min post-irradiation (P < 0.05). Inconsistently, ARID1A knock-down did not affect it, and SNF5 knock-down increased heterochromatin γH2AX at 1 Gy 60 min post-irradiation (P < 0.05). Moreover, YAP/TAZ knock-down decreased heterochromatin γH2AX 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 heterochromatin γH2AX 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 knock-down promoted γH2AX 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.
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