A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage.

TitleA chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage.
Publication TypeJournal Article
Year of Publication2010
AuthorsChou, DM, Adamson, B, Dephoure, NE, Tan, X, Nottke, AC, Hurov, KE, Gygi, SP, Colaiácovo, MP, Elledge, SJ
JournalProc Natl Acad Sci U S A
Volume107
Issue43
Pagination18475-80
Date Published2010 Oct 26
ISSN1091-6490
KeywordsAnimals, Caenorhabditis elegans, Chromatin, DNA Damage, DNA Repair, HeLa Cells, Humans, In Vitro Techniques, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Polycomb-Group Proteins, Proteomics, Repressor Proteins, Ultraviolet Rays
Abstract

Many proteins that respond to DNA damage are recruited to DNA lesions. We used a proteomics approach that coupled isotopic labeling with chromatin fractionation and mass spectrometry to uncover proteins that associate with damaged DNA, many of which are involved in DNA repair or nucleolar function. We show that polycomb group members are recruited by poly(ADP ribose) polymerase (PARP) to DNA lesions following UV laser microirradiation. Loss of polycomb components results in IR sensitivity of mammalian cells and Caenorhabditis elegans. PARP also recruits two components of the repressive nucleosome remodeling and deacetylase (NuRD) complex, chromodomain helicase DNA-binding protein 4 (CHD4) and metastasis associated 1 (MTA1), to DNA lesions. PARP plays a role in removing nascent RNA and elongating RNA polymerase II from sites of DNA damage. We propose that PARP sets up a transient repressive chromatin structure at sites of DNA damage to block transcription and facilitate DNA repair.

DOI10.1073/pnas.1012946107
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID20937877
PubMed Central IDPMC2972950
Grant ListR01GM058012 / GM / NIGMS NIH HHS / United States
R01 GM072551 / GM / NIGMS NIH HHS / United States
HG3456 / HG / NHGRI NIH HHS / United States
R01GM072551 / GM / NIGMS NIH HHS / United States
R01 GM058012 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R01 HG003456 / HG / NHGRI NIH HHS / United States