title: Structural and functional characterization of a cell cycle associated HDAC1/2 complex reveals the structural basis for complex assembly and nucleosome targeting.
abstract: Recent proteomic studies have identified a novel histone deacetylase complex that is upregulated during mitosis and is associated with cyclin A. This complex is conserved from nematodes to man and contains histone deacetylases 1 and 2, the MIDEAS corepressor protein and a protein called DNTTIP1 whose function was hitherto poorly understood. Here, we report the structures of two domains from DNTTIP1. The amino-terminal region forms a tight dimerization domain with a novel structural fold that interacts with and mediates assembly of the HDAC1:MIDEAS complex. The carboxy-terminal domain of DNTTIP1 has a structure related to the SKI/SNO/DAC domain, despite lacking obvious sequence homology. We show that this domain in DNTTIP1 mediates interaction with both DNA and nucleosomes. Thus, DNTTIP1 acts as a dimeric chromatin binding module in the HDAC1:MIDEAS corepressor complex.
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors: Toshimasa
authors: T
authors: Itoh
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors: Louise
authors: L
authors: Fairall
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors: Frederick W
authors: FW
authors: Muskett
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors: Charles P
authors: CP
authors: Milano
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors: Peter J
authors: PJ
authors: Watson
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors: Nadia
authors: N
authors: Arnaudo
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors: Almutasem
authors: A
authors: Saleh
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors: Christopher J
authors: CJ
authors: Millard
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
authors: Mohammed
authors: M
authors: El-Mezgueldi
authors: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors: Fabrizio
authors: F
authors: Martino
authors: Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK john.schwabe@le.ac.uk.
authors: John W R
authors: JW
authors: Schwabe
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002453:Cell Cycle; D056970:Co-Repressor Proteins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C436745:DNTTIP1 protein, human; C000598190:MIDEAS protein, human; D009687:Nuclear Proteins; D009707:Nucleosomes; D014157:Transcription Factors; D004247:DNA; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
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