Molecular function of ATM related TELI gene

RFC 5基因编码酿酒酵母复制因子C（RFC）复合物的一个小亚基。我们以前已经表明，温度敏感性（TS）rfc 5 -1突变在S期检查点受损。在这份报告中，我们表明，rfc 5 -1突变是敏感的DNA损伤剂。RFC 5对于减缓响应DNA损伤的S期进展速率是必需的。在S期rfc 5 -1突变体中，必需的中枢转导子Rad 53蛋白激酶的磷酸化响应于DNA损伤而减少。此外，响应于DNA损伤的RNR 3转录的诱导依赖于RFC 5。研究表明，Rad 53的磷酸化受共济失调毛细血管扩张突变（ATM）激酶亚家族成员Mec 1和Tel 1的控制。我们还表明，TEL 1的过表达抑制rfc 5 -1突变体的ts生长缺陷和DNA损伤敏感性，并恢复Rad 53和RNR 3诱导的磷酸化，以响应rfc 5 -1中的DNA损伤。我们的研究结果，再加上观察到过表达的RAD 53抑制缺陷的rfc 5 -1突变，表明Rfc 5是一种机制的一部分，转导的DNA损伤信号的激活中央换能器Rad 53。

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.