Regulatory mechanism of the protein complex involved in the integrity of telomere functions

参与端粒功能完整性的蛋白质复合物的调控机制

• 批准号: 18370006
• 负责人: MATSUURA Akira
• 金额: $ 11.58万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18370006/
• 关键词: ゲノム恒常性; 染色体; テロメア; 細胞周期; 出芽酵母; ATMファミリー; Cdk; CST複合体; Stn1; Cdc13; キャッピング複合体; 細胞周期制御; ATM; ATR; Cdc14; リン酸化

Telomere is an essential chromosomal element that composes of the end of eukaryotic linear chromosome and plays a role in the maintenance of its integrity. Dual functions of the telomere are to discriminate normal chromosomal ends from abnormal damaged ends, and to provide the field to replicate the end through the specific telomerase-mediated system. In this study, we aim to elucidate how the two antagonistic functions of the telomere are coordinated during the cell cycle.CST (Cdc13-Stn1-Ten1) complex of the budding yeast Saccharomyces cerevisiae has been shown to associate with the telomeric DNA ends and to be involved in the both functions of the telomere. We found that the CST complex was phosphorylated orderly by ATM kinases, that detect shorter telomeres, and by Cdk, that regulates cell cycle events. Moreover, we found that Stn1 was important for modulation of replication restart after replication forks arrested by the addition of hydroxyurea. Finally, we identified a novel alleles of STN1 whose product was defective in its protective role, and showed that coordination of N-terminal protective function with C-terminal replicative function was pivotal for cell viability in this mutant. Together, our results indicated that CST was regulated by a variety of signaling cascades to modify the function of the complex, thereby maintaining the integrity of the telomeres.

端粒是组成真核线性染色体末端的重要染色体元件，在维持其完整性方面发挥作用。端粒的双重功能是区分正常的染色体末端和异常受损的末端，并通过特定的端粒酶介导的系统提供复制末端的场所。在本研究中，我们旨在阐明端粒的两种拮抗功能在细胞周期中如何协调。芽殖酵母酿酒酵母的 CST (Cdc13-Stn1-Ten1) 复合物已被证明与端粒 DNA 末端相关联，并参与端粒的这两种功能。我们发现 CST 复合物被检测较短端粒的 ATM 激酶和调节细胞周期事件的 Cdk 有序磷酸化。此外，我们发现 Stn1 对于通过添加羟基脲阻止复制叉后复制重启的调节很重要。最后，我们鉴定了 STN1 的一个新等位基因，其产物在保护作用方面存在缺陷，并表明 N 端保护功能与 C 端复制功能的协调对于该突变体中的细胞活力至关重要。总之，我们的结果表明，CST 受到多种信号级联的调节，以改变复合物的功能，从而维持端粒的完整性。

项目成果

Regulation of replicative life span by multiple factors : lessons from molecular studies by the use of model systems

多重因素调节复制寿命：使用模型系统进行分子研究的教训

• 发表时间: 2007
• 作者: Akio;Nakashima;Yoshiko;Maruki;Yuko;Imamura;Chika;Kondo;Tomoko;Kawamata;Ippei;Kawanishi;Hideki;Takata;Akira;Matsuura;Kyung S.;Lee;Ushio;Kikkawa;Yoshinori;Ohsumi;Kazuyoshi;Yonezawa;Yoshiaki;Kamada;松浦彰;松浦彰;Yusuke Sakai;Aiko Matsui;Aiko Matsui;大井麻紗子;永野愛;富永卓弥;松井愛子;上村佳代;松井愛子;松井愛子;松浦彰;Lan Xiang,;浅野 敏;Akira Matsuura
• 通讯作者: Akira Matsuura

Molecular mechanism of autophagy induced by telomere-driven senescence in Saccharomyces cerevisiae.

酿酒酵母端粒驱动衰老诱导自噬的分子机制。

• 发表时间: 2009
• 作者: Akio;Nakashima;Yoshiko;Maruki;Yuko;Imamura;Chika;Kondo;Tomoko;Kawamata;Ippei;Kawanishi;Hideki;Takata;Akira;Matsuura;Kyung S.;Lee;Ushio;Kikkawa;Yoshinori;Ohsumi;Kazuyoshi;Yonezawa;Yoshiaki;Kamada;松浦彰;松浦彰;Yusuke Sakai;Aiko Matsui
• 通讯作者: Aiko Matsui

A chemical genetic approach reveals multiple pathways regulating longevity in budding yeast

化学遗传方法揭示了调节芽殖酵母寿命的多种途径

• 发表时间: 2008
• 作者: 原野純;広瀬恵子;上野 裕則;上野 裕則;上野 裕則;Kimihiko Sugaya;菅谷公彦;Kimihiko Sugaya;Akio Nakashima et al.;上村佳代;上村佳代;松井愛子;松井愛子;松井愛子;松浦彰
• 通讯作者: 松浦彰

脳内老化制御とバイオマーカー-基盤研究と食品素材

衰老控制和大脑生物标志物 - 基础研究和食品材料

• 发表时间: 2009
• 作者: Akira;Matsuura;Satoshi;Asano;松浦彰;松浦彰;松浦彰
• 通讯作者: 松浦彰

抗老化転写因子活性化剤及びその利用

抗衰老转录因子激活剂及其用途

• 发表时间: 2008