DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae
DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae
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DOI：
10.1073/pnas.96.7.3824
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发表时间：
1999-03-30
影响因子：
11.1
通讯作者：
Elledge, SJ
中科院分区：
文献类型：
--
作者：
Wang, H;Elledge, SJ
除了DNA聚合酶复合物外，DNA复制还需要一系列蛋白的协同作用，包括调节因子Cdc28/Clb和Dbf4/Cdc7激酶、Ores、Mcms、Cdc6、Cdc45和Dpb11。其中，作为BRCT重复序列的重要蛋白，Dpb11一直是一个谜。与DPB11基因相互作用的POL2基因与裂糖菌pombe同源物切割5也与DNA复制检查点有关。在这里，我们描述了一个基因，DRC1，作为dpb11-1的剂量抑制基因，DRC1是DNA复制所必需的细胞周期调节基因。我们发现Dpb11和Drc1都是s期检查点所必需的，包括响应DNA损伤和复制阻断的Rad53激酶的适当激活。Dpb11是第二个显示控制Rad53功能的brct重复蛋白，可能表明这类蛋白具有一般功能。DRC1和DPB11表现出合成致死性和剂量互抑性。Drc1和Dpb11蛋白在物理上相互关联，共同协调DNA复制和细胞周期。
In addition to DNA polymerase complexes, DNA replication requires the coordinate action of a series of proteins, including regulators Cdc28/Clb and Dbf4/Cdc7 kinases, Ores, Mcms, Cdc6, Cdc45, and Dpb11, Of these, Dpb11, an essential BRCT repeat protein, has remained particularly enigmatic. The Schizosaccharomyces pombe homolog of DPB11, cut5, has been implicated in the DNA replication checkpoint as has the POL2 gene with which DPB11 genetically interacts. Here we describe a gene, DRC1, isolated as a dosage suppressor of dpb11-1, DRC1 is an essential cell cycle-regulated gene required for DNA replication. We show that both Dpb11 and Drc1 are required for the S-phase checkpoint, including the proper activation of the Rad53 kinase in response to DNA damage and replication blocks. Dpb11 is the second BRCT-repeat protein shown to control Rad53 function, possibly indicating a general function for this class of proteins. DRC1 and DPB11 show synthetic lethality and reciprocal dosage suppression. The Drc1 and Dpb11 proteins physically associate and function together to coordinate DNA replication and the cell cycle.