Genome-wide role of Rad26 in promoting transcription-coupled nucleotide excision repair in yeast chromatin.

Proceedings of the National Academy of Sciences of the United States of America
Mingrui DuanPeng Mao

Abstract

Transcription-coupled nucleotide excision repair (TC-NER) is an important DNA repair mechanism that removes RNA polymerase (RNAP)-stalling DNA damage from the transcribed strand (TS) of active genes. TC-NER deficiency in humans is associated with the severe neurological disorder Cockayne syndrome. Initiation of TC-NER is mediated by specific factors such as the human Cockayne syndrome group B (CSB) protein or its yeast homolog Rad26. However, the genome-wide role of CSB/Rad26 in TC-NER, particularly in the context of the chromatin organization, is unclear. Here, we used single-nucleotide resolution UV damage mapping data to show that Rad26 and its ATPase activity is critical for TC-NER downstream of the first (+1) nucleosome in gene coding regions. However, TC-NER on the transcription start site (TSS)-proximal half of the +1 nucleosome is largely independent of Rad26, likely due to high occupancy of the transcription initiation/repair factor TFIIH in this nucleosome. Downstream of the +1 nucleosome, the combination of low TFIIH occupancy and high occupancy of the transcription elongation factor Spt4/Spt5 suppresses TC-NER in Rad26-deficient cells. We show that deletion of SPT4 significantly restores TC-NER across the genome in ...Continue Reading

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Citations

Aug 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Dong Wang
Dec 10, 2020·International Journal of Molecular Sciences·Mingrui DuanPeng Mao
Nov 20, 2020·Nature Reviews. Molecular Cell Biology·Melvin Noe GonzalezJesper Q Svejstrup
Mar 21, 2021·Applied Microbiology and Biotechnology·Lahiru N Jayakody, Yong-Su Jin
May 19, 2021·Genome Research·Kaitlynne A BohmJohn J Wyrick
May 29, 2021·NAR Genomics and Bioinformatics·Fernando PozoMichael L Tress
Jun 11, 2021·Nature Cell Biology·Marit E GeijerJurgen A Marteijn
Aug 21, 2021·DNA Repair·Liam Gaul, Jesper Q Svejstrup

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