title: UV induced ubiquitination of the yeast Rad4-Rad23 complex promotes survival by regulating cellular dNTP pools.
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.
authors.affiliation: Institute of Cancer & Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK College of Biology, Hunan University, Changsha 410082, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Institute of Cancer & Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK New York University Department of Biology,1009 Silver Center, 100 Washington Square East, NY, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Humphryes
authors.affiliation: Institute of Cancer & Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: van Eijk
authors.affiliation: Institute of Cancer & Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: Raymond
authors.initials: R
authors.lastname: Waters
authors.affiliation: Institute of Cancer & Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK Cambridge Epigenetix, Jonas Webb Building, Babraham Campus, Cambridge, CB22 3AT, UK.
authors.forename: Shirong
authors.initials: S
authors.lastname: Yu
authors.affiliation: North West Cancer Research Institute, Bangor University, Brambell Building, Bangor, LL57 2UW, UK.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kraehenbuehl
authors.affiliation: North West Cancer Research Institute, Bangor University, Brambell Building, Bangor, LL57 2UW, UK.
authors.forename: Edgar
authors.initials: E
authors.lastname: Hartsuiker
authors.affiliation: Institute of Cancer & Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK reedsh1@cardiff.ac.uk.
authors.forename: Simon H
authors.initials: SH
authors.lastname: Reed
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D014466:Ultraviolet Rays; D015003:Yeasts / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects
chemical_list: D004268:DNA-Binding Proteins; D003854:Deoxyribonucleotides; D005656:Fungal Proteins; D044767:Ubiquitin-Protein Ligases