Histone variant Htz1 promotes histone H3 acetylation to enhance nucleotide excision repair in Htz1 nucleosomes.
Nucleotide excision repair (NER) is critical for maintaining genome integrity. How chromatin dynamics are regulated to facilitate this process in chromatin is still under exploration. We show here that a histone H2A variant, Htz1 (H2A.Z), in nucleosomes has a positive function in promoting efficient NER in yeast. Htz1 inherently enhances the occupancy of the histone acetyltransferase Gcn5 on chromatin to promote histone H3 acetylation after UV irradiation. Consequently, this results in an increased binding of a NER protein, Rad14, to damaged DNA. Cells without Htz1 show increased UV sensitivity and defective removal of UV-induced DNA damage in the Htz1-bearing nucleosomes at the repressed MFA2 promoter, but not in the HMRa locus where Htz1 is normally absent. Thus, the effect of Htz1 on NER is specifically relevant to its presence in chromatin within a damaged region. The chromatin accessibility to micrococcal nuclease in the MFA2 promoter is unaffected by HTZ1 deletion. Acetylation on previously identified lysines of Htz1 plays little role in NER or cell survival after UV. In summary, we have identified a novel aspect of chromatin that regulates efficient NER, and we provide a model for how Htz1 influences NER in Htz1 nucleosomes.
Institute of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK and Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester M13 9PT, UK.
Yachuan
Y
Yu
Yanbo
Y
Deng
Simon H
SH
Reed
Catherine B
CB
Millar
Raymond
R
Waters
D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000235:genetics; D002843:Chromatin / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D017353:Gene Deletion; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics; D050296:Microbial Viability; D009707:Nucleosomes / Q000378:metabolism*; D010675:Pheromones / Q000235:genetics; D011401:Promoter Regions, Genetic; D011740:Pyrimidine Dimers / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D000099224:p300-CBP-Associated Factor
D000251:Adenosine Triphosphatases; D002843:Chromatin; D045643:DNA Repair Enzymes; D051548:Histone Acetyltransferases; D006657:Histones; D008074:Lipoproteins; D009707:Nucleosomes; D010675:Pheromones; D011740:Pyrimidine Dimers; D029701:Saccharomyces cerevisiae Proteins; C493530:Htz1 protein, S cerevisiae; C095063:MFA2 protein, S cerevisiae; C072975:RAD14 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C481261:Swr1 protein, S cerevisiae