Chromosome stability and cellular senescence in yeast aging gene project

酵母衰老基因项目中的染色体稳定性和细胞衰老

• 批准号: 10832006
• 负责人: KIKUCHI Akihiko
• 金额: $ 2.18万
• 依托单位: NAGOYA University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10832006/
• 关键词: yeast; aging; heterochromatin; nucleolus; HTR1; SGS1; SIR; DNA topoisomerases; 酵母; 老化; UTH4; エージング・アッセイ; フロキシン; MCS1; SSD1; テロメア; GFPたんぱく

1 : Aging mechanism by yeast HTR1 geneThe products of two genes, HTR1 and SGS1 are suggested to involve in the cellular aging process in yeast. We constructed a double mutant and found that two genes were epistatic. The fusion product of HTR1p with GFP was localized in the cytoplasm. The deletion of HTR1 gene conferred the ultra sensitivity to hydroxyurea, and this sensitive phenotype was rescued by one of the multi copy suppressor of htr1 mutant. Since this suppressor gene product was shown as a corepressor particularly for the genes in heterochromatin region associated with SIR complex, the senescence signal must be transmitted from HTR1 to SIR and finally to the genes in heterochromatin.2 : Function of SGS1 geneThe product of another aging gene SGS1 was shown to interact with DNA topoisomerases. To visualize the alteration of chromosome structure and the extent to cellular senescence, we marked various fragments of DNA topoisomerases with GFP. Among these fusion product, some showed strong affinity to nucleolus, rather than to chromosomes. The genetical meaning of this observation is yet to be investigated, but we got very interesting clue to understand nucleolus function in aging process in relation to DNA topoisomerases.

1：酵母Htr1基因的衰老机制，提示两个基因的Htr1和SGS1产物涉及酵母中的细胞衰老过程。我们构建了一个双突变体，发现两个基因是上毒的。 HTR1P与GFP的融合产物位于细胞质中。 HTR1基因的缺失赋予了对羟基脲的超灵敏度，并且这种灵敏的表型是由HTR1突变体的多拷贝抑制剂之一救出的。由于该抑制剂基因产物被显示为核压剂，特别是针对与爵士复合物相关的异染色质区域的基因，因此必须将衰老信号从HTR1传播到Sir，最后向异染料素中的基因传播到杂丝蛋白中的基因。为了可视化染色体结构的改变和对细胞衰老的程度，我们用GFP标记了DNA拓扑异构酶的各种片段。在这些融合产物中，有些对核仁表现出很强的亲和力，而不是染色体。该观察结果的遗传含义尚待研究，但是我们有非常有趣的线索可以理解与DNA拓扑酶相关的衰老过程中的核仁功能。

项目成果

K.-H. KIM et al.: "Cloning and characterization of the gene encoding Aspergillus nidulans"GENE. 236. 293-301 (1999)

K.-H。

S. KATO and A. KIKUCHI: "DNA Topoisomerase : The key enzyme that regulates DNA super structure"Nagoya Journal of Medical Science. 61. 11-26 (1998)

S. KATO 和 A. KIKUCHI：“DNA 拓扑异构酶：调节 DNA 超结构的关键酶”名古屋医学杂志。

K. SUGIMOTO et al.: "Temporal and spatial distribution of DNA topoisomerase II alters during proliferation"Blood. 91. 1407-1417 (1998)

K. SUGIMOTO 等人：“DNA 拓扑异构酶 II 的时间和空间分布在增殖过程中发生变化”血液。

K. NAGATA et al.: "Cellular localization and expression of template-activating factor I in different cell"Experimental Cell Research. 240. 274-281 (1998)

K. NAGATA 等：“模板激活因子 I 在不同细胞中的细胞定位和表达”实验细胞研究。

K.NAGATA et al.: "Cellular localization and expression of template-activating factor lin different cell types" Experimental Cell Research. 240. 274-281 (1998)

K.NAGATA 等人：“模板激活因子在不同细胞类型中的细胞定位和表达”实验细胞研究。