title: UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation.
abstract: Histone H2B monoubiquitylation plays an important role in RNA polymerase II (RNAPII) elongation. Whether this modification responds to RNAPII stalling is not yet known. We report that both yeast and human cells undergo a rapid and significant H2B deubiquitylation after exposure to UV irradiation. This deubiquitylation occurs concurrently with UV-induced transcription arrest and is significantly reduced in a DNA damage-bypassing RNAPII yeast mutant. Consistent with these results, yeast deubiquitylases Ubp8 and Ubp10 are associated with the RNAPII complex. Moreover, simultaneous deletion of Ubp8 and Ubp10 leads to a lack of H2B deubiquitylation after UV exposure. Consequently, nucleotide excision repair at an actively transcribed gene locus is decreased, whereas UV-induced RNAPII degradation is increased in ubp8Δubp10Δ mutant cells. These results indicate that eukaryotic cells respond to RNAPII arrest by deubiquitylating H2B to coordinate DNA repair and RNAPII degradation.
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520.
authors.forename: Peng
authors.initials: P
authors.lastname: Mao
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520.
authors.forename: Rithy
authors.initials: R
authors.lastname: Meas
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Dorgan
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520 smerdon@wsu.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Smerdon
mesh_terms: D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D012319:RNA Polymerase II; D010450:Endopeptidases; C403282:UBP10 protein, S cerevisiae; D043222:Ubiquitin Thiolesterase; C503322:UBP8 protein, S cerevisiae
keywords: chromatin; epigenetics; nucleosome; transcription-coupled repair