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Identification of genes that affect sensitivity to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae

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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.

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Acknowledgments

We thank Dr. A. Kikuchi (Nagoya University) for providing us with yeast strains, and Dr. A. Sakai, (Mitsubishi Kasei Institute of Life Sciences) for providing us with YEp MPT5. This work was partly supported by the grant for 2008 Strategic Research Project (W20015) of Yokohama City University, Japan.

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  1. Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan

    Michihiko Fujii, Kensuke Miki, Shinichi Takayama & Dai Ayusawa

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  1. Michihiko Fujii
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  2. Kensuke Miki
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  3. Shinichi Takayama
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  4. Dai Ayusawa
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Correspondence to Michihiko Fujii.

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Communicated by T. Ito.

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Fujii, M., Miki, K., Takayama, S. et al. Identification of genes that affect sensitivity to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae . Mol Genet Genomics 283, 461–468 (2010). https://doi.org/10.1007/s00438-010-0535-6

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  • DOI: https://doi.org/10.1007/s00438-010-0535-6

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