Open AccessCDC7-independent G1/S transition revealed by targeted protein degradation
Author(s) -
Jan M. Suski,
Nalin Ratnayeke,
Marcin Braun,
Tian Zhang,
Vladislav Strmiska,
Wojciech Michowski,
Geylani Can,
Antoine Simoneau,
Konrad Snioch,
Mikolaj Cup,
Caitlin Sullivan,
Xiumei Wu,
Joanowacka,
Timothy B. Branigan,
Lindsey R. Pack,
James A. DeCaprio,
Yan Geng,
Lee Zou,
Steven P. Gygi,
Johannes C. Walter,
Tobias Meyer,
Piotr Siciński
Publication year - 2022
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-022-04698-x
Subject(s) - cyclin dependent kinase 1 , microbiology and biotechnology , cell cycle , dna re replication , dna replication , eukaryotic dna replication , biology , s phase , cyclin dependent kinase 2 , kinase , control of chromosome duplication , cell division , cyclin dependent kinase , protein kinase a , chemistry , cell , dna , biochemistry
The entry of mammalian cells into the DNA synthesis phase (S phase) represents a key event in cell division 1 . 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.