Title | A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Chou, DM, Adamson, B, Dephoure, NE, Tan, X, Nottke, AC, Hurov, KE, Gygi, SP, Colaiácovo, MP, Elledge, SJ |
Journal | Proc Natl Acad Sci U S A |
Volume | 107 |
Issue | 43 |
Pagination | 18475-80 |
Date Published | 2010 Oct 26 |
ISSN | 1091-6490 |
Keywords | Animals, 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 | <p>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.</p> |
DOI | 10.1073/pnas.1012946107 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 20937877 |
PubMed Central ID | PMC2972950 |
Grant List | R01GM058012 / GM / NIGMS NIH HHS / United States / HHMI / Howard Hughes Medical Institute / 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 R01 HG003456 / HG / NHGRI NIH HHS / United States |