title: Identification of genes that affect sensitivity to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae.
abstract: Small molecules that exhibit biological effects have been successfully used to study various biological phenomena. 5-Bromodeoxyuridine (BrdU) is a thymidine analog that affects various biological processes, such as cellular differentiation and cellular senescence in cultured mammalian cells. Although BrdU is thought to modulate these phenomena by changing chromatin structure and gene expression, the molecular mechanisms for the action of BrdU are not understood well. To analyze the molecular mechanisms of BrdU with genetic methods, we used the yeast Saccharomyces cerevisiae as a model. Our genetic screening has revealed that a defect in MPT5/HTR1/UTH4/PUF5 led to an increased sensitivity to BrdU, and that overexpression of VHT1 or SDT1 led to resistance to BrdU. The increased sensitivity to BrdU caused by a defect in MPT5 was suppressed by a mutation in SIR2, SIR3, or SIR4, which is involved in chromatin silencing and transcriptional repression. These findings suggest that chromatin silencing proteins are involved in the modulation of the cellular phenomena by BrdU, and would provide clues to answer the old question of how BrdU affects various biological phenomena.
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan. mifuji@yokohama-cu.ac.jp
authors.forename: Michihiko
authors.initials: M
authors.lastname: Fujii
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takayama
authors.forename: Dai
authors.initials: D
authors.lastname: Ayusawa
mesh_terms: D001483:Base Sequence; D001973:Bromodeoxyuridine / Q000378:metabolism / Q000494:pharmacology*; D018628:Gene Dosage / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics*; D016153:Genes, Suppressor; D005820:Genetic Testing; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009995:Osmosis / Q000187:drug effects; D010957:Plasmids / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013012:Sorbitol / Q000494:pharmacology; D013489:Suppression, Genetic / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
chemical_list: C449502:MPT5 protein, S cerevisiae; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D013012:Sorbitol; D001973:Bromodeoxyuridine; D013936:Thymidine