N-terminal short fragment of TUP1 confers resistance to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae
N-terminal short fragment of TUP1 confers resistance to 5-bromodeoxyuridine in the yeast Saccharomyces cerevisiae
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DOI：
10.1016/j.bbrc.2011.06.064
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发表时间：
2011-07-22
影响因子：
3.1
通讯作者：
Ayusawa, Dai
中科院分区：
文献类型：
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作者：
Takayama, Shinichi;Fujii, Michihiko;Ayusawa, Dai
表现出生物活性的小分子有助于理解各种生物现象的分子机制。5-溴脱氧尿苷（BrdU）是一种胸苷类似物，可调节多种生物学现象，如培养的哺乳动物细胞中的细胞分化和细胞衰老。虽然BrdU被认为通过改变染色质结构和基因表达发挥作用，但其精确的分子机制尚不清楚。为了研究BrdU作用的分子机制，我们采用酿酒酵母作为模型系统，并筛选多拷贝抑制基因，赋予耐BrdU。我们的遗传筛选揭示了TUP 1的N-末端短片段的表达，以及与TUP 1相互作用的组蛋白脱乙酰酶HDA 1或HOS 1的破坏，赋予了对BrdU的抗性。这些结果表明，染色质蛋白的BrdU的功能的含义，并将提供新的线索，以回答老问题的BrdU如何调节各种生物现象。(C)2011 Elsevier Inc. All rights reserved.
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. (C) 2011 Elsevier Inc. All rights reserved.