UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation

Peng Mao; Rithy Meas; Kathleen M Dorgan; Michael J Smerdon

doi:10.1073/pnas.1403901111

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UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation

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UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation

Peng Mao, Rithy Meas, Kathleen M Dorgan and Michael J Smerdon

Proceedings of the National Academy of Sciences - PNAS, Vol.111(35), pp.12811-12816

09/02/2014

DOI: https://doi.org/10.1073/pnas.1403901111

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https://hdl.handle.net/2376/110946

PMCID: PMC4156752

PMID: 25136098

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Abstract

Endopeptidases - metabolism

Cockayne Syndrome - metabolism

Saccharomyces cerevisiae - genetics

Humans

Cells, Cultured

DNA Repair - physiology

Ubiquitin - metabolism

Nucleosomes - metabolism

Epigenesis, Genetic - radiation effects

Nuclear Proteins - metabolism

RNA Polymerase II - metabolism

Saccharomyces cerevisiae Proteins - genetics

Ultraviolet Rays - adverse effects

Saccharomyces cerevisiae - metabolism

DNA Damage - physiology

Epigenesis, Genetic - genetics

Cockayne Syndrome - genetics

Saccharomyces cerevisiae Proteins - metabolism

Ubiquitin Thiolesterase - metabolism

RNA Polymerase II - genetics

Histones - metabolism

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.

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Title: UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation
Creators: Peng Mao - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520
Rithy Meas - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520
Kathleen M Dorgan - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520
Michael J Smerdon - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520 smerdon@wsu.edu
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.111(35), pp.12811-12816
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R37 ES002614 / NIEHS NIH HHS R01 ES002614 / NIEHS NIH HHS ES002614 / NIEHS NIH HHS
Identifiers: 99900547218501842
Language: English
Resource Type: Journal article