The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway
The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway
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DOI：
10.1073/pnas.94.26.14361
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发表时间：
1997-12-23
影响因子：
11.1
通讯作者：
Koshland, D
中科院分区：
文献类型：
--
作者：
Cohen-Fix, O;Koshland, D
DNA 复制的抑制和物理 DNA 损伤会诱导检查点反应，从而在两个不同阶段阻止细胞周期进程。在酿酒酵母中，两个检查点反应的执行都需要 Mec1 和 Rad53 蛋白。这一观察结果表明，这些检查点反应是通过共同的信号转导途径介导的。然而，由于检查点诱导的停滞发生在不同的细胞周期阶段，介导这些停滞的下游效应器可能是不同的。我们之前已经证明，酿酒酵母蛋白 Pds1p 是一种后期抑制剂，对于在存在 DNA 损伤的情况下有丝分裂中的细胞周期停滞至关重要。在此，我们证明 DNA 损伤而不是 DNA 复制的抑制会诱导 Pds1p 的磷酸化。对不同检查点突变体中 Pds1p 磷酸化的分析表明，在 DNA 损伤存在的情况下，Pds1p 以 Mec1p 和 Rad9p 依赖性但 Rad53p 独立的方式磷酸化。我们的数据将 Pds1p 和 Rad53p 置于 DNA 损伤检查点通路的平行分支上。我们认为 Pds1p 是 DNA 损伤检查点途径的下游靶标，并且它参与实施 DNA 损伤检查点抑制，特别是在有丝分裂中。
Inhibition of DNA replication and physical DNA damage induce checkpoint responses that arrest cell cycle progression at two different stages. In Saccharomyces cerevisiae, the execution of both checkpoint responses requires the Mec1 and Rad53 proteins. This observation led to the suggestion that these checkpoint responses are mediated through a common signal transduction pathway. However, because the checkpoint-induced arrests occur at different cell cycle stages, the downstream effecters mediating these arrests are likely to be distinct. We have previously shown that the S. cerevisiae protein Pds1p is an anaphase inhibitor and is essential for cell cycle arrest in mitosis in the presence DNA damage. Herein we show that DNA damage, but not inhibition of DNA replication, induces the phosphorylation of Pds1p. Analyses of Pds1p phosphorylation in different checkpoint mutants reveal that in the presence of DNA damage, Pds1p is phosphorylated in a Mec1p- and Rad9p-dependent but Rad53p-independent manner. Our data place Pds1p and Rad53p on parallel branches of the DNA damage checkpoint pathway. We suggest that Pds1p is a downstream target of the DNA damage checkpoint pathway and that it is involved in implementing the DNA damage checkpoint arrest specifically in mitosis.