Histone acetylation, chromatin remodelling and nucleotide excision repair: hint from the study on MFA2 in Saccharomyces cerevisiae.
Nucleotide excision repair (NER) is a sophisticated repair pathway that the cell utilizes to remove a broad range of DNA damage to help maintain the functional integrity of the genome. In the context of DNA packaged into chromosomes it is clear that the NER machinery does not repair all regions with equal efficiency. Recently, we found after UV that histone acetylation and chromatin remodelling were activated. UV irradiation triggers genome-wide histone hyperacetylation at both histone H3 and H4. However, in nucleosomes at the repressed MFA2 promoter only histone H3, but not histone H4, is hyperacetylated following UV. This Gcn5p-mediated histone H3 hyperacetylation enables efficient NER at MFA2. Chromatin in this promoter also becomes more accessible after UV. This is not dependent on Gcn5p, yet it is partially dependent on Swi2p. In later repair times both events gradually return to the pre-UV state. The post-UV histone modifications and chromatin remodelling at the repressed MFA2 promoter do not activate MFA2 transcription, nor do they require damage recognition by Rad4p or Rad14p. These experiments indicate early events are triggered in chromatin in response to UV treatment, and they are likely needed for efficient NER.
Yu
Yachuan
Y
Department of Pathology, School of Medicine, Cardiff University, Cardiff, UK.
Waters
Raymond
R
D000107:Acetylation; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D002875:Chromosomes / Q000648:ultrastructure; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004261:DNA Replication; D004307:Dose-Response Relationship, Radiation; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000737:chemistry*; D008074:Lipoproteins / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D009711:Nucleotides / Q000737:chemistry*; D010675:Pheromones; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D000099224:p300-CBP-Associated Factor
D002843:Chromatin; D004247:DNA; D045643:DNA Repair Enzymes; D051548:Histone Acetyltransferases; D006657:Histones; D008074:Lipoproteins; D009707:Nucleosomes; D009711:Nucleotides; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; C095063:MFA2 protein, S cerevisiae; C072975:RAD14 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor