Functional and physical interaction between Rad24 and Rfc5 in the yeast checkpoint pathways
Functional and physical interaction between Rad24 and Rfc5 in the yeast checkpoint pathways
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DOI：
10.1128/mcb.18.9.5485
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发表时间：
1998-09-01
影响因子：
5.3
通讯作者：
Sugimoto, K
中科院分区：
文献类型：
--
作者：
Shimomura, T;Ando, S;Sugimoto, K
RFC 5基因编码酿酒酵母中复制因子C（RFC）复合物的一个小亚基，并且已被证明是响应复制阻断和DNA损伤的检查点所需的。在这里，我们描述了RAD 24的分离，已知在DNA损伤检查点中发挥作用，作为rfc 5 -1的剂量依赖性抑制剂。RAD 24过表达抑制rfc 5 -1细胞对DNA损伤剂的敏感性和DNA损伤诱导的Rad 53磷酸化缺陷。Rad 24与Rfc 5一样，是调节Rad 53磷酸化以响应DNA损伤所必需的。Rad 24蛋白在结构上与RFC亚基相关，与RFC亚基Rfc 2和Rfc 5物理相互作用，并与Rfc 5共沉积。尽管单独的rad 24 Delta突变不会导致复制阻断检查点的缺陷，但它确实增强了rfc 5 -1突变体中的缺陷。此外，RAD 24的过表达抑制复制阻断检查点中的rfc 5 -1缺陷。综上所述，我们的研究结果证明了Rad 24和Rfc 5在检查点通路中的物理和功能相互作用。
The RFC5 gene encodes a small subunit of replication factor C (RFC) complex in Saccharomyces cerevisiae and has been shown to be required for the checkpoints which respond to replication block and DNA damage. Here we describe the isolation of RAD24, known to play a role in the DNA damage checkpoint, as a dosage-dependent suppressor of rfc5-1. RAD24 overexpression suppresses the sensitivity of rfc5-1 cells to DNA dam aging agents and the defect in DNA damage-induced Rad53 phosphorylation. Rad24, like Rfc5, is required for the regulation of Rad53 phosphorylation in response to DNA damage. The Rad24 protein, which is structurally related to the RFC subunits, interacts physically with RFC subunits Rfc2 and Rfc5 and cosediments,vith Rfc5. Although the rad24 Delta mutation alone does not cause a defect in the replication block checkpoint, it does enhance the defect in rfc5-1 mutants. Furthermore, overexpression of RAD24 suppresses the rfc5-1 defect in the replication block checkpoint. Taken together, our results demonstrate a physical and functional interaction between Rad24 and Rfc5 in the checkpoint pathways.