Title: An intrinsic S/G2 checkpoint enforced by ATR.

Authors: Saldivar, Joshua C; Hamperl, Stephan; Bocek, Michael J; Chung, Mingyu; Bass, Thomas E; Cisneros-Soberanis, Fernanda; Samejima, Kumiko; Xie, Linfeng; Paulson, James R; Earnshaw, William C; Cortez, David; Meyer, Tobias; Cimprich, Karlene A

Published In Science, (2018 08 24)

Abstract: 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 G1/S, G2/M, and metaphase/anaphase transitions, but thus far, no control mechanism has been identified for the S/G2 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/G2 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/G2 checkpoint.

PubMed ID: 30139873

MeSH Terms: No MeSH terms associated with this publication