title: Contributions of histone H3 nucleosome core surface mutations to chromatin structures, silencing and DNA repair.
abstract: Histone H3 mutations in residues that cluster in a discrete region on the nucleosome surface around lysine 79 of H3 affect H3-K79 methylation, impair transcriptional silencing in subtelomeric chromatin, and reveal distinct contributions of histone H3 to various DNA-damage response and repair pathways. These residues might act by recruitment of silencing and DNA-damage response factors. Alternatively, their location on the nucleosome surface suggests a possible involvement in nucleosome positioning, stability and nucleosome interactions. Here, we show that the yeast H3 mutants hht2-T80A, hht2-K79E, hht2-L70S, and hht2-E73D show normal nucleosome positioning and stability in minichromosomes. However, loss of silencing in a subtelomeric URA3 gene correlates with a shift of the promoter nucleosome, while nucleosome positions and stability in the coding region are maintained. Moreover, the H3 mutants show normal repair of UV lesions by photolyase and nucleotide excision repair in minichromosomes and slightly enhanced repair in the subtelomeric region. Thus, these results support a role of those residues in the recruitment of silencing proteins and argue against a general role in nucleosome organization.
authors: Department of Biology, Institute of Cell Biology, ETH Zurich, Zurich, Switzerland.
authors: Michel
authors: M
authors: Fink
authors: Jeffrey S
authors: JS
authors: Thompson
authors: Fritz
authors: F
authors: Thoma
mesh_terms: D015825:Chromosomes, Fungal / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D004278:DNA, Superhelical / Q000378:metabolism; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000378:metabolism; D020868:Gene Silencing / Q000528:radiation effects; D006657:Histones / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009707:Nucleosomes / Q000235:genetics* / Q000528:radiation effects; D016366:Open Reading Frames / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011740:Pyrimidine Dimers / Q000378:metabolism / Q000528:radiation effects; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D016615:Telomere / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D004278:DNA, Superhelical; D006657:Histones; D009707:Nucleosomes; D011740:Pyrimidine Dimers; D029701:Saccharomyces cerevisiae Proteins; C554167:URA3 protein, S cerevisiae; D004255:Deoxyribodipyrimidine Photo-Lyase