Distinct roles for RSC and SWI/SNF chromatin remodelers in genomic excision repair

Kaitlynne A. Bohm, Amelia J. Hodges, Wioletta Czaja, Kathiresan Selvam, Michael J. Smerdon, Peng Mao, John J. Wyrick

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1047-1059
Number of pages13
JournalGenome research
Volume31
Issue number6
DOIs
StatePublished - Jun 2021
Externally publishedYes

Bibliographical note

Funding Information:
We thank Mark Wildung and Wei Wei Du for technical assistance with Ion Proton sequencing. We thank Dr. Frank Holstege for providing yeast strains and Dr. David Shore for providing nucleosome coordinates. We thank Dr. Steven Roberts for providing purified T4 endonuclease V and Angelica Washington for helping to construct yeast strains. This research was supported by National Institute of Environmental Health Sciences grants R21ES027937 (to J.J.W.), R03ES027945 (to P.M.), R21ES029302 (to P.M. and J.J.W.), and R01ES028698 (to J.J.W. and M.J.S.). K.A.B. was funded by a National Institute of General Medical Sciences training grant (T32GM008336).

Publisher Copyright:
© 2021 Bohm et al.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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