HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins.
HDAC1 is a member of the histone deacetylase family, which plays an important role in modulating the eukaryotic chromatin structure. Numerous studies have demonstrated its involvement in transcription and in tumorigenesis. To better understand the functions and regulation of HDAC1, a yeast two-hybrid screening approach was chosen to identify novel interactions involving HDAC1. Human HDAC1 was found to interact specifically in yeast, mammalian cells, and in vitro with the human Hus1 gene product, whose Schizosaccharomyces pombe homolog has been implicated in G(2)/M checkpoint control. Both HDAC1 and Hus1 proteins localize to the nuclei. Furthermore, HDAC1 and Hus1 were found to exist in a complex with Rad9, a known Hus1-interacting factor. In addition, bioinformatics analysis of the protein sequences of Hus1, Rad1, and Rad9, three checkpoint Rad proteins that form a complex, revealed that they all contain a putative proliferating cell nuclear antigen (PCNA) fold, raising the possibility that these factors may bind to DNA in a PCNA-like ring structure. The results reported in this study strongly suggest a novel pathway involving HDAC1 in G(2)/M checkpoint control through the interaction with a functional Rad complex that may utilize a PCNA-like structure. Therefore, physically and functionally similar apparatus may function during G(2)/M checkpoint and DNA replication.
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Functional Genomics Area and the Biomolecular Structure and Computing, Core Technology Area, Novartis Pharmaceuticals Corporation, Summit, New Jersey 07901, USA.
Yan-Neale
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Cueto
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Xu
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Cohen
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D003001:Cloning, Molecular; D016195:G2 Phase; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008322:Mammals; D008938:Mitosis; D008969:Molecular Sequence Data; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D014162:Transfection
D018797:Cell Cycle Proteins; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D029702:Schizosaccharomyces pombe Proteins; C106332:hus1 protein, S pombe; C069930:rad9 protein; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases