title: Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4.
abstract: Ataxia telangiectasia mutated (ATM)- and Rad3-related protein (ATR) is a phosphatidylinositol-kinase (PIK)-related kinase that has been implicated in the response of human cells to multiple forms of DNA damage and may play a role in the DNA replication checkpoint. The purification of an ATR complex allowed identification of chromodomain-helicase-DNA-binding protein 4 (CHD4) as an ATR-associated protein by tandem mass spectrometric sequencing. CHD4 (also called Mi-2beta) is a component of a histone-deacetylase-2 (HDAC2)-containing complex, the nucleosome remodeling and deacetylating (NRD) complex. Endogenous ATR, CHD4, and HDAC2 are shown to coimmunoprecipitate, and ATR and HDAC2 coelute through two biochemical purification steps. Other members of the NRD complex, HDAC1, MTA1, and MTA2, are also detectable in ATR immunoprecipitates. ATR's association with CHD4 and HDAC2 suggests that there may be a linkage between ATR's role in mediating checkpoints induced by DNA damage and chromatin modulation via remodeling and deacetylation.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. schmidt@slsiris.harvard.edu
authors.forename: D R
authors.initials: DR
authors.lastname: Schmidt
authors.forename: S L
authors.initials: SL
authors.lastname: Schreiber
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D064007:Ataxia Telangiectasia Mutated Proteins; D001324:Autoantigens; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D004265:DNA Helicases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D004261:DNA Replication; D006367:HeLa Cells; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009707:Nucleosomes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D009707:Nucleosomes; D012097:Repressor Proteins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases