title: Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response.
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.
authors.affiliation: Department of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Andrew E H
authors.initials: AE
authors.lastname: Elia
authors.affiliation: Department of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Boardman
authors.affiliation: Department of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Huttlin
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Everley
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Dephoure
authors.affiliation: Department of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA.
authors.forename: Chunshui
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA.
authors.forename: Itay
authors.initials: I
authors.lastname: Koren
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.affiliation: Department of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA. Electronic address: selledge@genetics.med.harvard.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
mesh_terms: D000107:Acetylation / Q000528:radiation effects; D044842:Cullin Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D030562:Databases, Protein; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation / Q000528:radiation effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D040081:Protein Array Analysis / Q000706:statistics & numerical data; D020543:Proteome / Q000378:metabolism / Q000528:radiation effects; D040901:Proteomics / Q000379:methods* / Q000706:statistics & numerical data; D008941:Spindle Apparatus / Q000378:metabolism; D054875:Ubiquitination / Q000528:radiation effects
chemical_list: D044842:Cullin Proteins; D020543:Proteome; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; D046988:Proteasome Endopeptidase Complex; D045643:DNA Repair Enzymes