DOI: 10.1073/pnas.0807485106. The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks [Penn]

The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks

10.1073/pnas.0807485106

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

DNA double strand breaks (DSBs) initiate reversible cellular checkpoint and repair activities. Whereas many of the activating events at DSBs have recently been elucidated, the mechanisms used to terminate responses at these sites are largely undefined. Here we report a pathway required to reverse RNF8-Ubc13 dependent ubiquitination events on chromatin flanking DSBs. Inhibition of the Rap80-BRCC36 de-ubiquitinating enzyme complex partially restored DSB-associated ubiquitin levels following RNF8 knockdown or proteasome inhibition. Similarly, BRCC36 knockdown or expression of a BRCC36 de-ubiquitinating enzyme-inactive mutant rescued both 53BP1 recruitment to DSBs and ionizing radiation-induced γH2AX ubiquitination following RNF8 depletion, and mitigated ionizing radiation sensitivity resulting from RNF8 deficiency. Thus, concomitant and opposing RNF8-Ubc13 ubiquitin ligase and Rap80-BRCC36 ubiquitin hydrolysis activities are responsible for determining steady-state ubiquitin levels at DNA DSBs. These findings reveal a Rap80-BRCC36 dependent pathway that is required for appropriate DSB recruitment and repair responses.

Bibliography

Shao, G., Lilli, D. R., Patterson-Fortin, J., Coleman, K. A., Morrissey, D. E., & Greenberg, R. A. (2009). The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proceedings of the National Academy of Sciences, 106(9), 3166â3171.

Authors 6

Genze Shao (first)
Dana R. Lilli (additional)
Jeffrey Patterson-Fortin (additional)
Kara A. Coleman (additional)
Devon E. Morrissey (additional)
Roger A. Greenberg (additional)

References 36 Referenced 179

Dates

Type	When
Created	16 years, 6 months ago (Feb. 7, 2009, 4:03 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:20 p.m.)
Indexed	1 month ago (July 24, 2025, 7 a.m.)
Issued	16 years, 5 months ago (March 3, 2009)
Published	16 years, 5 months ago (March 3, 2009)
Published Online	16 years, 5 months ago (March 3, 2009)
Published Print	16 years, 5 months ago (March 3, 2009)

Funders 0

None

BibTeX

@article{Shao_2009, title={The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks}, volume={106}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0807485106}, DOI={10.1073/pnas.0807485106}, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Shao, Genze and Lilli, Dana R. and Patterson-Fortin, Jeffrey and Coleman, Kara A. and Morrissey, Devon E. and Greenberg, Roger A.}, year={2009}, month=mar, pages={3166–3171} }

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