小柯机器人

美国DanaFarber癌症研究所Piotr Sicinski、威尔康奈尔医学院Tobias Meyer等研究人员合作发现，靶向蛋白降解揭示不依赖CDC7的G1/S转换。相关论文于2022年5月4日发表在《自然》杂志上。

研究人员表明，CDC7对许多不同类型的细胞分裂是可有可无的，这是用化学遗传系统确定的，该系统能使CDC7在培养细胞和活小鼠中急性关闭。研究人员证明另一种细胞周期激酶CDK1在G1/S转换期间也是活跃的，无论是在循环细胞还是在退出静止期的细胞。结果表明，CDC7和CDK1在G1/S转换期间发挥着功能上冗余的作用，这些激酶中至少有一个必须存在才能进入S期。这些观察结果修正了人们对细胞周期进展的理解，表明CDK1在生理上调节着细胞分裂周期中两个不同的转变，而CDC7在DNA复制中具有一个冗余的功能。

据了解，哺乳动物细胞进入DNA合成期（S期）是细胞分裂的一个关键事件。根据目前的细胞周期模型，激酶CDC7与细胞周期蛋白依赖性激酶CDK2共同作用，构成了DNA复制的必要和限速触发器。

附：英文原文

Title: CDC7-independent G1/S transition revealed by targeted protein degradation

Author: Suski, Jan M., Ratnayeke, Nalin, Braun, Marcin, Zhang, Tian, Strmiska, Vladislav, Michowski, Wojciech, Can, Geylani, Simoneau, Antoine, Snioch, Konrad, Cup, Mikolaj, Sullivan, Caitlin M., Wu, Xiaoji, Nowacka, Joanna, Branigan, Timothy B., Pack, Lindsey R., DeCaprio, James A., Geng, Yan, Zou, Lee, Gygi, Steven P., Walter, Johannes C., Meyer, Tobias, Sicinski, Piotr

Issue&Volume: 2022-05-04

Abstract: The entry of mammalian cells into the DNA synthesis phase (Sphase) represents a key event in cell division1. According to current models of the cell cycle, the kinase CDC7 constitutes an essential and rate-limiting trigger of DNA replication, acting together with the cyclin-dependent kinase CDK2. Here we show that CDC7 is dispensable for cell division of many different cell types, as determined using chemical genetic systems that enable acute shutdown of CDC7 in cultured cells and in live mice. We demonstrate that another cell cycle kinase, CDK1, is also active during G1/S transition both in cycling cells and in cells exiting quiescence. We show that CDC7 and CDK1 perform functionally redundant roles during G1/S transition, and at least one of these kinases must be present to allow S-phase entry. These observations revise our understanding of cell cycle progression by demonstrating that CDK1 physiologically regulates two distinct transitions during cell division cycle, whereas CDC7 has a redundant function in DNA replication.

DOI: 10.1038/s41586-022-04698-x

Source: https://www.nature.com/articles/s41586-022-04698-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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