title: Histone modification and chromatin remodeling during NER.
abstract: Here we review our developments of and results with high resolution studies on global genome nucleotide excision repair (GG-NER) in Saccharomyces cerevisiae. Technologies were developed to examine NER at nucleotide resolution in yeast sequences of choice and to determine how these related to local changes in chromatin. We focused on how GG-NER relates to histone acetylation for its functioning and we identified the histone acetyltransferase Gcn5 and acetylation at lysines 9/14 of histone H3 as a major factor in enabling efficient repair. Factors influencing this Gcn5-mediated event are considered which include Rad16, a GG-NER specific SWI/SNF factor and the yeast histone variant of H2AZ (Htz1). We describe results employing primarily MFA2 as a model gene, but also those with URA3 located at subtelomeric sequences. In the latter case we also see a role for acetylation at histone H4. We then consider the development of a high resolution genome-wide approach that enables one to examine correlations between histone modifications and the NER of UV-induced cyclobutane pyrimidine dimers throughout entire yeast genome. This is an approach that will enable rapid advances in understanding the complexities of how compacted chromatin in chromosomes is processed to access DNA damage before it is returned to its pre-damaged status to maintain epigenetic codes.
authors.affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK; College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: WatersR1@cardiff.ac.uk.
authors.forename: Raymond
authors.initials: R
authors.lastname: Waters
authors.affiliation: Institute of Cancer and 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 and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. Electronic address: ReedSH1@cardiff.ac.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Reed
mesh_terms: D000107:Acetylation; D042002:Chromatin Assembly and Disassembly; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism; D042421:Histone Code; D006657:Histones / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D004271:DNA, Fungal; D051548:Histone Acetyltransferases; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor
keywords: Chromatin; Global genome nucleotide excision repair; Histone acetylation; Histone variant H2AX; Rad16; Saccharomyces cerevisiae; UV-induced cyclobutane pyrimidine dimers