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SWI/SNF染色质重塑复合物有助于解决R环介导的转录-复制冲突
2021-05-16 20:13

西班牙塞利维亚大学Andrés Aguilera研究组发现,SWI/SNF染色质重塑复合物有助于解决R环介导的转录-复制冲突。这一研究成果于2021年5月13日在线发表在国际学术期刊《自然—遗传学》上。

研究人员表示,ATP依赖的染色质重塑因子通常在人类癌症中发生突变。哺乳动物SWI/SNF复合物包含三个保守的多亚基染色质重塑因子(cBAF、ncBAF和PBAF),它们共享负责主要ATP酶活性的BRG1(也称为SMARCA4)亚基。BRG1是癌症中最常见的突变Snf2样ATP酶。

研究人员测试了SWI/SNF在基因组不稳定性中的作用,这是癌细胞的标志,它在转录、DNA复制和DNA损伤修复中起着重要作用。研究人员表明,敲除BRG1会增加R环和依赖R环的DNA断裂,以及转录-复制(T-R)冲突。如FANCD2位点所确定的,BRG1与R环和复制叉片段共定位,而BRG1的敲除对FANCD2沉默是上位的。这项研究扩展到了SWI/SNF的其他组分,揭示了SWI/SNF复合体(特别是cBAF)在帮助解决R环介导的T-R冲突中的关键作用,从而揭示了染色质重塑保护基因组完整性的新机制。

附:英文原文

Title: The SWI/SNF chromatin remodeling complex helps resolve R-loop-mediated transcription–replication conflicts

Author: Aleix Bayona-Feliu, Sonia Barroso, Sergio Muoz, Andrs Aguilera

Issue&Volume: 2021-05-13

Abstract: ATP-dependent chromatin remodelers are commonly mutated in human cancer. Mammalian SWI/SNF complexes comprise three conserved multisubunit chromatin remodelers (cBAF, ncBAF and PBAF) that share the BRG1 (also known as SMARCA4) subunit responsible for the main ATPase activity. BRG1 is the most frequently mutated Snf2-like ATPase in cancer. In the present study, we have investigated the role of SWI/SNF in genome instability, a hallmark of cancer cells, given its role in transcription, DNA replication and DNA-damage repair. We show that depletion of BRG1 increases R-loops and R-loop-dependent DNA breaks, as well as transcription–replication (T-R) conflicts. BRG1 colocalizes with R-loops and replication fork blocks, as determined by FANCD2 foci, with BRG1 depletion being epistatic to FANCD2 silencing. Our study, extended to other components of SWI/SNF, uncovers a key role of the SWI/SNF complex, in particular cBAF, in helping resolve R-loop-mediated T-R conflicts, thus, unveiling a new mechanism by which chromatin remodeling protects genome integrity.

DOI: 10.1038/s41588-021-00867-2

Source: https://www.nature.com/articles/s41588-021-00867-2

 

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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