Bibliographic Details
| Title: |
Genome-wide role of Rad26 in promoting transcription-coupled nucleotide excision repair in yeast chromatin. |
| Authors: |
Mingrui Duan1,2, Selvam, Kathiresan1, Wyrick, John J.1,3 jwyrick@wsu.edu, Peng Mao1,2 pmao@salud.unm.edu |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America. 8/4/2020, Vol. 117 Issue 31, p18608-18616. 9p. |
| Subject Terms: |
*CHROMATIN, *DNA repair, *TRANSCRIPTION factors, *RNA polymerases, *YEAST |
| 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 a rad26Δ mutant, particularly in the downstream nucleosomes. These data demonstrate that the requirement for Rad26 in TC-NER is modulated by the distribution of TFIIH and Spt4/Spt5 in transcribed chromatin and Rad26 mainly functions downstream of the +1 nucleosome to remove TC-NER suppression by Spt4/Spt5. [ABSTRACT FROM AUTHOR] |
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