CDK4/6 activity is required during G 2 arrest to prevent stress-induced endoreplication.

Autor:	McKenney C; Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; The Biochemistry, Cellular, and Molecular Biology Graduate Program, Johns Hopkins University, Baltimore, MD, USA., Lendner Y; Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Guerrero Zuniga A; Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; The Biochemistry, Cellular, and Molecular Biology Graduate Program, Johns Hopkins University, Baltimore, MD, USA., Sinha N; Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Veresko B; Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Aikin TJ; Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; The Biochemistry, Cellular, and Molecular Biology Graduate Program, Johns Hopkins University, Baltimore, MD, USA., Regot S; Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jazyk:	angličtina
Zdroj:	Science (New York, N.Y.) [Science] 2024 May 03; Vol. 384 (6695), pp. eadi2421. Date of Electronic Publication: 2024 May 03.
DOI:	10.1126/science.adi2421
Abstrakt:	Cell cycle events are coordinated by cyclin-dependent kinases (CDKs) to ensure robust cell division. CDK4/6 and CDK2 regulate the growth 1 (G 1 ) to synthesis (S) phase transition of the cell cycle by responding to mitogen signaling, promoting E2F transcription and inhibition of the anaphase-promoting complex. We found that this mechanism was still required in G 2 -arrested cells to prevent cell cycle exit after the S phase. This mechanism revealed a role for CDK4/6 in maintaining the G 2 state, challenging the notion that the cell cycle is irreversible and that cells do not require mitogens after passing the restriction point. Exit from G 2 occurred during ribotoxic stress and was actively mediated by stress-activated protein kinases. Upon relief of stress, a significant fraction of cells underwent a second round of DNA replication that led to whole-genome doubling.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.