HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G(2)/M checkpoint Rad proteins

HDAC1 is a member of the histone deacetylase family, which plays an importa nt 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-hybri d screening approach was chosen to identify novel interactions involving HD AC1. Human HDAC1 was found to interact specifically in yeast, mammalian cel ls, and irt vitro with the human Hus1 gene product, whose Schizosaccharomyc es pombe homolog has been implicated in G(2)/M checkpoint control. Both HDA C1 and Hus1 proteins localize to the nuclei. Furthermore, HDAC1 and Hus1 we re 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 tha t they all contain a putative proliferating cell nuclear antigen (PCNA) fol d, raising the possibility that these factors may bind to DNA in a PCNA-lik e ring structure. The results reported in this study strongly suggest a nov el pathway involving HDAC1 in G(2)/M checkpoint control through the interac tion with a functional Rad complex that may utilize a PCNA-like structure. Therefore, physically and functionally similar apparatus may function durin g G(2)/M checkpoint and DNA replication.