An intrinsic S/G 2 checkpoint enforced by ATR.

Autor: Saldivar JC; Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA., Hamperl S; Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA., Bocek MJ; Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA., Chung M; Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA., Bass TE; Department of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Avenue, Nashville, TN 37232, USA., Cisneros-Soberanis F; Wellcome Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, UK.; Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México; Insituto Nacional de Cancerología, México City 14080, Mexico., Samejima K; Wellcome Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, UK., Xie L; Department of Chemistry, University of Wisconsin-Oshkosh, 800 Algoma Boulevard, Oshkosh, WI 54901, USA., Paulson JR; Department of Chemistry, University of Wisconsin-Oshkosh, 800 Algoma Boulevard, Oshkosh, WI 54901, USA., Earnshaw WC; Wellcome Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, UK., Cortez D; Department of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Avenue, Nashville, TN 37232, USA., Meyer T; Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA., Cimprich KA; Department of Chemical and Systems Biology, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5441, USA. cimprich@stanford.edu.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2018 Aug 24; Vol. 361 (6404), pp. 806-810.
DOI: 10.1126/science.aap9346
Abstrakt: The cell cycle is strictly ordered to ensure faithful genome duplication and chromosome segregation. Control mechanisms establish this order by dictating when a cell transitions from one phase to the next. Much is known about the control of the G 1 /S, G 2 /M, and metaphase/anaphase transitions, but thus far, no control mechanism has been identified for the S/G 2 transition. Here we show that cells transactivate the mitotic gene network as they exit the S phase through a CDK1 (cyclin-dependent kinase 1)-directed FOXM1 phosphorylation switch. During normal DNA replication, the checkpoint kinase ATR (ataxia-telangiectasia and Rad3-related) is activated by ETAA1 to block this switch until the S phase ends. ATR inhibition prematurely activates FOXM1, deregulating the S/G 2 transition and leading to early mitosis, underreplicated DNA, and DNA damage. Thus, ATR couples DNA replication with mitosis and preserves genome integrity by enforcing an S/G 2 checkpoint.
(Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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