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

Jan M. Suski, Nalin Ratnayeke, Marcin Braun, Tian Zhang, Vladislav Strmiska, Wojciech Michowski, Geylani Can, Antoine Simoneau, Konrad Snioch, Mikolaj Cup, Caitlin M. Sullivan, Xiaoji Wu, Joanna Nowacka, Timothy B. Branigan, Lindsey R. Pack, James A. DeCaprio, Yan Geng, Lee Zou, Steven P. Gygi, Johannes C. Walter, Tobias Meyer () and Piotr Sicinski ()
Additional contact information
Jan M. Suski: Dana–Farber Cancer Institute
Nalin Ratnayeke: Weill Cornell Medicine
Marcin Braun: Dana–Farber Cancer Institute
Tian Zhang: Harvard Medical School
Vladislav Strmiska: Dana–Farber Cancer Institute
Wojciech Michowski: Dana–Farber Cancer Institute
Geylani Can: Harvard Medical School
Antoine Simoneau: Harvard Medical School
Konrad Snioch: Dana–Farber Cancer Institute
Mikolaj Cup: Dana–Farber Cancer Institute
Caitlin M. Sullivan: Dana–Farber Cancer Institute
Xiaoji Wu: Dana–Farber Cancer Institute
Joanna Nowacka: Dana–Farber Cancer Institute
Timothy B. Branigan: Dana–Farber Cancer Institute, Harvard Medical School
Lindsey R. Pack: Weill Cornell Medicine
James A. DeCaprio: Dana–Farber Cancer Institute, Harvard Medical School
Yan Geng: Dana–Farber Cancer Institute
Lee Zou: Harvard Medical School
Steven P. Gygi: Harvard Medical School
Johannes C. Walter: Harvard Medical School
Tobias Meyer: Weill Cornell Medicine
Piotr Sicinski: Dana–Farber Cancer Institute

Nature, 2022, vol. 605, issue 7909, 357-365

Abstract: Abstract The entry of mammalian cells into the DNA synthesis phase (S phase) 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.

Date: 2022
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DOI: 10.1038/s41586-022-04698-x

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