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首页> 外文期刊>Cell cycle >The conserved C terminus of Claspin interacts with Rad9 and promotes rapid activation of Chk1
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The conserved C terminus of Claspin interacts with Rad9 and promotes rapid activation of Chk1

机译：Claspin的保守C末端与Rad9相互作用并促进Chk1的快速激活

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摘要

Claspin is a key mediator of the ATR-Chk1 checkpoint pathway. In response to DNA damage, Claspin interacts with Rad17 and Chk1 in a phosphorylation- dependent manner, enabling ATR to phosphorylate Chk1 efficiently. Claspin also interacts with Rad9, but how they interact and whether the interaction is functional remains unknown. Unexpectedly, our analysis of two splicing isoforms of Claspin provided an answer to these questions. The Claspin 1339 isoform contains an evolutionarily conserved C terminus, but the Claspin 1332 isoform does not. Although the transcripts encoding both Claspin isoforms coexist in HCT116 cells, Claspin 1339 is the predominant form responsible for Chk1 activation. When expressed in cells depleted of endogenous Claspin, both Claspin 1339 and Claspin 1332 are able to mediate Chk1 activation. However, the activation of Chk1 is delayed in Claspin 1332-expressing cells compared with Claspin 1339-expressing cells. Furthermore, only Claspin 1339 but not Claspin 1332 interacts with Rad9 efficiently. Together, these results suggest that the conserved C terminus of Claspin interacts with Rad9 and ensures timely activation of the ATR-Chk1 pathway.
机译：Claspin是ATR-Chk1检查站途径的关键介体。响应于DNA损伤，Claspin以依赖磷酸化的方式与Rad17和Chk1相互作用，从而使ATR能够有效地磷酸化Chk1。 Claspin还与Rad9交互，但是如何交互以及交互是否起作用尚不清楚。出乎意料的是，我们对Claspin的两个剪接同工型的分析为这些问题提供了答案。 Claspin 1339亚型包含一个进化保守的C末端，而Claspin 1332亚型则不含。尽管编码这两种Claspin同工型的转录物共存于HCT116细胞中，但Claspin 1339是负责Chk1激活的主要形式。当在缺乏内源性Claspin的细胞中表达时，Claspin 1339和Claspin 1332都能够介导Chk1激活。但是，与表达Claspin 1339的细胞相比，在表达Claspin 1332的细胞中Chk1的激活被延迟。此外，只有Claspin 1339可以有效地与Rad9交互，而Claspin 1332则不可以。总之，这些结果表明，Claspin的保守C末端与Rad9相互作用，并确保及时激活ATR-Chk1途径。

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