Chromatin modifications and nucleotide excision repair.
We have developed an innovative approach to examine the incidence and frequency of repair of UV-induced cyclobutane pyrimidine dimers at nucleotide resolution in yeast sequences of choice and have then adapted it for the footprinting of nucleosomes and regulatory proteins that bind to DNA. Using the mating-type-specific gene MFA2 as a model, we have determined DNA repair rates for individual DNA lesions throughout the sequence. Positioned nucleosomes occur when the gene is repressed and we have begun to unravel how they are modified after UV. This radiation triggers histone acetylation, primarily at H3, and is mediated by the Gcn5 histone acetyltransferase; its absence reduces repair substantially. UV also triggers chromatin remodelling as measured by increased accessibility of restriction sites at the cores of the two nucleosomes in the gene's upstream control region; this is partly mediated by Swi2, a yeast SWI/SNF factor. Surprisingly neither of these events require functional NER, but NER is needed to return the chromatin to its pre-UV state.
Waters
Raymond
R
Pathology Department, Cardiff University, School of Medicine, Heath Park, Cardiff.
Reed
Simon H
SH
Yu
Yachuan
Y
Teng
Yumin
Y
D002843:Chromatin / Q000378:metabolism* / Q000528:radiation effects; D042002:Chromatin Assembly and Disassembly; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal; D006657:Histones / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009707:Nucleosomes; C072975:RAD14 protein, S cerevisiae; C493797:Rad4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D045643:DNA Repair Enzymes