Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response

Andrew E.H. Elia, Alexander P. Boardman, David C. Wang, Edward L. Huttlin, Robert A. Everley, Noah Dephoure, Chunshui Zhou, Itay Koren, Steven P. Gygi, Stephen J. Elledge

Research output: Contribution to journalArticlepeer-review

258 Scopus citations

Abstract

Execution of the DNA damage response (DDR) relies upon a dynamic array of protein modifications. Using quantitative proteomics, we have globally profiled ubiquitination, acetylation, and phosphorylation in response to UV and ionizing radiation. To improve acetylation site profiling, we developed the strategy FACET-IP. Our datasets of 33,500 ubiquitination and 16,740 acetylation sites provide valuable insight into DDR remodeling of the proteome. We find that K6- and K33-linked polyubiquitination undergo bulk increases in response to DNA damage, raising the possibility that these linkages are largely dedicated to DDR function. We also show that Cullin-RING ligases mediate 10% of DNA damage-induced ubiquitination events and that EXO1 is an SCF-Cyclin F substrate in the response to UV radiation. Our extensive datasets uncover additional regulated sites on known DDR players such as PCNA and identify previously unknown DDR targets such as CENPs, underscoring the broad impact of the DDR on cellular physiology. Elia et al. have globally profiled ubiquitination, acetylation, and phosphorylation in the DNA damage response (DDR). Their valuable datasets of 33,500 ubiquitination and 16,740 acetylation sites implicate K6- and K33-linked polyubiquitination in the DDR, demonstrate that CRLs mediate 10% of DDR ubiquitination events, and reveal that EXO1 is an SCF-Cyclin F substrate.

Original languageEnglish
Pages (from-to)867-881
Number of pages15
JournalMolecular Cell
Volume59
Issue number5
DOIs
StatePublished - 3 Sep 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

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