title: How chromatin is remodelled during DNA repair of UV-induced DNA damage in Saccharomyces cerevisiae.
abstract: Global genome nucleotide excision repair removes DNA damage from transcriptionally silent regions of the genome. Relatively little is known about the molecular events that initiate and regulate this process in the context of chromatin. We've shown that, in response to UV radiation-induced DNA damage, increased histone H3 acetylation at lysine 9 and 14 correlates with changes in chromatin structure, and these alterations are associated with efficient global genome nucleotide excision repair in yeast. These changes depend on the presence of the Rad16 protein. Remarkably, constitutive hyperacetylation of histone H3 can suppress the requirement for Rad7 and Rad16, two components of a global genome repair complex, during repair. This reveals the connection between histone H3 acetylation and DNA repair. Here, we investigate how chromatin structure is modified following UV irradiation to facilitate DNA repair in yeast. Using a combination of chromatin immunoprecipitation to measure histone acetylation levels, histone acetylase occupancy in chromatin, MNase digestion, or restriction enzyme endonuclease accessibility assays to analyse chromatin structure, and finally nucleotide excision repair assays to examine DNA repair, we demonstrate that global genome nucleotide excision repair drives UV-induced chromatin remodelling by controlling histone H3 acetylation levels in chromatin. The concerted action of the ATPase and C3HC4 RING domains of Rad16 combine to regulate the occupancy of the histone acetyl transferase Gcn5 on chromatin in response to UV damage. We conclude that the global genome repair complex in yeast regulates UV-induced histone H3 acetylation by controlling the accessibility of the histone acetyl transferase Gcn5 in chromatin. The resultant changes in histone H3 acetylation promote chromatin remodelling necessary for efficient repair of DNA damage. Recent evidence suggests that GCN5 plays a role in NER in human cells. Our work provides important insight into how GG-NER operates in chromatin.
authors.affiliation: Department of Medical Genetics, Haematology, and Pathology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Shirong
authors.initials: S
authors.lastname: Yu
authors.forename: Yumin
authors.initials: Y
authors.lastname: Teng
authors.forename: Raymond
authors.initials: R
authors.lastname: Waters
authors.forename: Simon H
authors.initials: SH
authors.lastname: Reed
mesh_terms: D000107:Acetylation / Q000528:radiation effects; D000251:Adenosine Triphosphatases / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D017353:Gene Deletion; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010675:Pheromones / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D000099224:p300-CBP-Associated Factor
chemical_list: D000251:Adenosine Triphosphatases; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D008074:Lipoproteins; D009687:Nuclear Proteins; D010675:Pheromones; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C095063:MFA2 protein, S cerevisiae; C063915:RAD7 protein, S cerevisiae; C066502:TUP1 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C075467:RAD16 protein, S cerevisiae