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Cell Rep. 2013 Nov 27;5(4):1095-107. doi: 10.1016/j.celrep.2013.10.027. Epub 2013 Nov 21.

ATR activates the S-M checkpoint during unperturbed growth to ensure sufficient replication prior to mitotic onset.

Author information

1
Genome Stability Laboratory, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Ireland.
2
Genome Stability Laboratory, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Ireland. Electronic address: noel.lowndes@nuigalway.ie.

Abstract

Cells must accurately replicate and segregate their DNA once per cell cycle in order to successfully transmit genetic information. During S phase in the presence of agents that cause replication stress, ATR-dependent checkpoints regulate origin firing and the replication machinery as well as prevent untimely mitosis. Here, we investigate the role of ATR during unperturbed growth in vertebrate cells. In the absence of ATR, individual replication forks progress more slowly, and an increased number of replication origins are activated. These cells also enter mitosis early and divide more rapidly, culminating in chromosome bridges and laggards at anaphase, failed cytokinesis, and cell death. Interestingly, cell death can be rescued by prolonging mitosis with partial inhibition of the mitotic cyclin-dependent kinase 1. Our data indicate that one of the essential roles of ATR during normal growth is to minimize the level of unreplicated DNA before the onset of mitosis.

PMID:
24268773
DOI:
10.1016/j.celrep.2013.10.027
[Indexed for MEDLINE]
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