title: N-terminal short fragment of TUP1 confers resistance to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae.
abstract: Small molecules that exhibit biological activity have contributed to the understanding of the molecular mechanisms of various biological phenomena. 5-Bromodeoxyuridine (BrdU) is a thymidine analogue that modulates various biological phenomena such as cellular differentiation and cellular senescence in cultured mammalian cells. Although BrdU is thought to function through changing chromatin structure and gene expression, its precise molecular mechanisms are not understood. To study the molecular mechanism for the action of BrdU, we have employed the yeast Saccharomyces cerevisiae as a model system, and screened multi-copy suppressor genes that confer resistance to BrdU. Our genetic screen has revealed that expression of the N-terminal short fragment of TUP1, and also disruption of HDA1 or HOS1, histone deacetylases that interact with TUP1, conferred resistance to BrdU. These results suggest the implication of the chromatin proteins in the function of BrdU, and would provide novel clues to answer the old question of how BrdU modulates various biological phenomena.
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-Ku, Yokohama, Kanagawa 236 0027, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takayama
authors.forename: Michihiko
authors.initials: M
authors.lastname: Fujii
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miki
authors.forename: Dai
authors.initials: D
authors.lastname: Ayusawa
mesh_terms: D001973:Bromodeoxyuridine / Q000494:pharmacology*; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C065455:CYC8 protein, S cerevisiae; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; C499673:HDA1 protein, S cerevisiae; D006655:Histone Deacetylases; D001973:Bromodeoxyuridine