Distinct roles for RSC and SWI/SNF chromatin remodelers in genomic excision repair.
Distinct roles for RSC and SWI/SNF chromatin remodelers in genomic excision repair.
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DOI：
10.1101/gr.274373.120
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发表时间：
2021-06
期刊：
影响因子：
7
通讯作者：
Wyrick JJ
中科院分区：
文献类型：
--
作者：
Bohm KA;Hodges AJ;Czaja W;Selvam K;Smerdon MJ;Mao P;Wyrick JJ
核小体是紫外线损伤修复的重要障碍，因为它们阻碍了核苷酸切除修复(NER)对损伤的识别。RSC和SWI/SNF染色质重构体在细胞中的作用是通过移动或驱逐核小体来促进DNA访问，这两个都与酵母中的NER相连。在这里，我们报告了紫外线诱导的环丁烷嘧啶二聚体(CPD)在缺乏RSC或SWI/SNF活性的酵母细胞中的全基因组修复图谱。我们的数据表明，SWI/SNF通常不是NER所必需的，而是促进特定酵母基因上CPD损伤的修复。相反，RSC亚基的突变或缺失会导致酵母基因组中NER的普遍缺陷。我们的数据表明，RSC不仅在核小体DNA中修复，而且在邻近的连接子DNA和核小体无性区(NFR)中也需要修复。尽管RSC催化亚基的耗尽也会影响N-甲基嘌呤(NMP)损伤的碱基切除修复(BER)，但RSC的活性对接头DNA和NFR中的BER不那么重要。此外，我们的数据表明，RSC在转录DNA的转录偶联NER(TC-NER)中起着直接作用。这些发现有助于确定每个染色质重构体在DNA修复中所处的特定基因组和染色质环境，并表明RSC在促进两个NER亚途径的修复方面发挥着独特的功能。
Nucleosomes are a significant barrier to the repair of UV damage because they impede damage recognition by nucleotide excision repair (NER). The RSC and SWI/SNF chromatin remodelers function in cells to promote DNA access by moving or evicting nucleosomes, and both have been linked to NER in yeast. Here, we report genome-wide repair maps of UV-induced cyclobutane pyrimidine dimers (CPDs) in yeast cells lacking RSC or SWI/SNF activity. Our data indicate that SWI/SNF is not generally required for NER but instead promotes repair of CPD lesions at specific yeast genes. In contrast, mutation or depletion of RSC subunits causes a general defect in NER across the yeast genome. Our data indicate that RSC is required for repair not only in nucleosomal DNA but also in neighboring linker DNA and nucleosome-free regions (NFRs). Although depletion of the RSC catalytic subunit also affects base excision repair (BER) of N-methylpurine (NMP) lesions, RSC activity is less important for BER in linker DNA and NFRs. Furthermore, our data indicate that RSC plays a direct role in transcription-coupled NER (TC-NER) of transcribed DNA. These findings help to define the specific genomic and chromatin contexts in which each chromatin remodeler functions in DNA repair, and indicate that RSC plays a unique function in facilitating repair by both NER subpathways.
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5.6
作者：
Czaja W;Mao P;Smerdon MJ
通讯作者：
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影响因子：
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作者：
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