Molecular function of ATM related TELI gene

ATM相关TELI基因的分子功能

• 批准号: 09680673
• 负责人: SUGIMOTO Katsunori
• 金额: $ 1.47万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680673/
• 关键词: DNA damage; cheekpoint; DNA複製

The RFC5 gene encodes a small subunit of replication factor C (RFC) complex in Saccharomyces cerevisiae. We have previously shown that a temperature-sensitive (ts) rfc5-1 mutation is impaired in the S phase checkpoint. In this report, we show that the rfc5-1 mutation is sensitive to DNA-damaging agents. RFC5 is necessary for slowing down the rate of S phase progression in response to DNA damage. The phosphorylation of the essential central transducer, Rad53 protein kinase, is reduced in response to DNA damage in rfc5-1 mutants during the S phase. Furthermore, the inducibility of RNR3 transcription in response to DNA damage is dependent on RFC5. It has been shown that phosphorylation of Rad53 is controlled by Mec1 and Tel1, members of the subfamily of ataxia telangiectasia mutated (ATM) kinases. We also demonstrate that overexpression of TEL1 suppresses the ts growth defect and DNA damage sensitivity of rfc5-1 mutants and restores phosphorylation of Rad53 and RNR3 induction in response to DNA damage in rfc5-1. Our results, together with the observation that overexpression of RAD53 suppresses the defects of the rfc5-1 mutation, suggest that Rfc5 is part of a mechanism transducing the DNA damage signal to the activation of the central transducer Rad53.

RFC5 基因编码酿酒酵母中复制因子 C (RFC) 复合物的一个小亚基。我们之前已经证明，温度敏感 (ts) rfc5-1 突变在 S 期检查点中受到损害。在本报告中，我们表明 rfc5-1 突变对 DNA 损伤剂敏感。 RFC5 对于减缓 DNA 损伤引起的 S 期进展速度是必要的。 rfc5-1 突变体在 S 期期间，由于 DNA 损伤，必需的中枢转导因子 Rad53 蛋白激酶的磷酸化会降低。此外，RNR3 转录对 DNA 损伤的诱导能力依赖于 RFC5。研究表明，Rad53 的磷酸化受 Mec1 和 Tel1 控制，Mec1 和 Tel1 是共济失调毛细血管扩张突变 (ATM) 激酶亚家族的成员。我们还证明，TEL1 的过表达可抑制 rfc5-1 突变体的 ts 生长缺陷和 DNA 损伤敏感性，并恢复 Rad53 和 RNR3 诱导的磷酸化，以响应 rfc5-1 中的 DNA 损伤。我们的结果，加上 RAD53 过度表达抑制 rfc5-1 突变缺陷的观察结果表明，Rfc5 是将 DNA 损伤信号转导至中央传感器 Rad53 激活的机制的一部分。

项目成果

Kondo,T.et al.: "Role of complex containing Rad17,Mec3 and Ddcl in the yeast DNA damage check point path way." Mol.Cell.Biol.19. 1136-1143 (1999)

Kondo,T.et al.：“含有 Rad17、Mec3 和 Ddcl 的复合物在酵母 DNA 损伤检查点路径中的作用。”

K.Sugimoto: "Rfc5,replication factor C component, is regulred for regulation of Rad 53 protein Kinase in the check point pathway" Mol.Cell.Biol. 17. 5905-5914 (1997)

K.Sugimoto：“Rfc5，复制因子 C 成分，在检查点通路中调节 Rad 53 蛋白激酶”Mol.Cell.Biol。

Shimomura,T.et al.: "Functional and physical interaction between Rad24 and Rfc5 in the yeast check point path ways." Mol.Cell.Biol.18. 5485-5491 (1998)

Shimomura,T.et al.：“酵母检查点路径中 Rad24 和 Rfc5 之间的功能和物理相互作用。”

Sugimoto, K.et al.: "Rfc5,replication factor C component,is reguised for regulation of Rod53 Protein Kinase in the yeast checkpoint pathway." Mol.Cell.Biol. 17. 5905-5914 (1997)

Sugimoto, K. 等人：“Rfc5（复制因子 C 成分）被用于调节酵母检查点通路中的 Rod53 蛋白激酶。”

Shimomura, T.et al.: "Punctional and physical interaction between Rad24 and Rfc5 in the yeast checkpoint pathways." Mol.Cell.Biol. 18. 5485-5491 (1998)

Shimomura, T.et al.：“酵母检查点通路中 Rad24 和 Rfc5 之间的功能和物理相互作用。”