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首页> 外文期刊>Nucleus >Evidence for a mammalian late-G1 phase inhibitor of replication licensing distinct from geminin or Cdk activity
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Evidence for a mammalian late-G1 phase inhibitor of replication licensing distinct from geminin or Cdk activity

机译：哺乳动物晚期G1期复制许可抑制剂的证据与geminin或Cdk活性不同

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Pre-replication complexes (pre-RCs) are assembled onto DNA during late mitosis and G1 to license replication origins for use in S phase. In order to prevent re-replication of DNA, licensing must be completely shutdown prior to entry into S phase. While mechanisms preventing re-replication during S phase and mitosis have been elucidated, the means by which cells first prevent licensing during late G1 phase are poorly understood. We have employed a hybrid mammalian / Xenopus egg extract replication system to dissect activities that inhibit replication licensing at different stages of the cell cycle in Chinese Hamster Ovary (CHO) cells. We find that soluble extracts from mitotic cells inhibit licensing through a combination of geminin and Cdk activities, while extracts from S-phase cells inhibit licensing predominantly through geminin alone. Surprisingly however, geminin did not accumulate until after cells enter S phase. Unlike extracts from cells in early G1 phase, extracts from late G1 phase and early S phase cells contained an inhibitor of licensing that could not be accounted for by either geminin or Cdk. Moreover, inhibiting cyclin and geminin protein synthesis or inhibiting Cdk activity early in G1 phase did not prevent the appearance of inhibitory activity. These results suggest that a soluble inhibitor of replication licensing appears prior to entry into S phase that is distinct from either geminin or Cdk activity. Our hybrid system should permit the identification of this and other novel cell cycle regulatory activities.
机译：复制前复合物（pre-RCs）在有丝分裂晚期和G1期间组装到DNA上，以许可复制起点用于S期。为了防止DNA重复复制，必须在进入S阶段之前完全关闭许可。尽管已经阐明了防止在S期和有丝分裂期间进行复制的机制，但人们对细胞在G1期后期首先防止许可的手段了解甚少。我们采用了混合的哺乳动物/非洲爪蟾卵提取物复制系统来剖析抑制中国仓鼠卵巢（CHO）细胞在细胞周期不同阶段复制许可的活性。我们发现有丝分裂细胞的可溶性提取物通过结合geminin和Cdk活性抑制许可，而S期细胞的提取物主要通过geminin抑制许可。然而，令人惊讶的是，直到细胞进入S期后双胚蛋白才开始积累。与早期G1期细胞提取物不同，早期G1期细胞和S期早期细胞提取物含有一种许可抑制剂，而双胍或Cdk均不能解释这种许可。此外，在G1期早期抑制细胞周期蛋白和双胚蛋白的合成或抑制Cdk的活性不会阻止抑制活性的出现。这些结果表明，可溶性许可的复制许可抑制剂在进入S期之前就出现了，这不同于geminin或Cdk的活性。我们的混合系统应允许识别这种和其他新颖的细胞周期调节活性。

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