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UV induced ubiquitination of the yeast Rad4–Rad23 complex promotes survival by regulating cellular dNTP pools

Zhou, Zheng, Humphryes, Neil, Van Eijk, Patrick, Waters, Raymond, Yu, Shirong, Kraehenbuehl, Rolf, Hartsuiker, Edgar and Reed, Simon H. 2015. UV induced ubiquitination of the yeast Rad4–Rad23 complex promotes survival by regulating cellular dNTP pools. Nucleic Acids Research 43 (15) , pp. 7360-7370. 10.1093/nar/gkv680

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Abstract

Regulating gene expression programmes is a central facet of the DNA damage response. The Dun1 kinase protein controls expression of many DNA damage induced genes, including the ribonucleotide reductase genes, which regulate cellular dNTP pools. Using a combination of gene expression profiling and chromatin immunoprecipitation, we demonstrate that in the absence of DNA damage the yeast Rad4–Rad23 nucleotide excision repair complex binds to the promoters of certain DNA damage response genes including DUN1, inhibiting their expression. UV radiation promotes the loss of occupancy of the Rad4–Rad23 complex from the regulatory regions of these genes, enabling their induction and thereby controlling the production of dNTPs. We demonstrate that this regulatory mechanism, which is dependent on the ubiquitination of Rad4 by the GG-NER E3 ligase, promotes UV survival in yeast cells. These results support an unanticipated regulatory mechanism that integrates ubiquitination of NER DNA repair factors with the regulation of the transcriptional response controlling dNTP production and cellular survival after UV damage.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Additional Information: This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: Oxford University Press
ISSN: 0305-1048
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 22 June 2015
Last Modified: 10 Jun 2020 10:30
URI: http://orca-mwe.cf.ac.uk/id/eprint/84172

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