Atr activates the s-m checkpoint during unperturbed growth to ensure sufficient replication prior to mitotic onset
Eykelenboom, John Kenneth Harte, Emma Christina Canavan, Lynn Pastor-Peidro, Ana Calvo-Asensio, Irene Llorens-Agost, Marta Lowndes, Noel Francis
Eykelenboom, John Kenneth
Harte, Emma Christina
Canavan, Lynn
Pastor-Peidro, Ana
Calvo-Asensio, Irene
Llorens-Agost, Marta
Lowndes, Noel Francis
Repository DOI
Publication Date
2013-11-01
Type
Article
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Citation
Eykelenboom, John Kenneth; Harte, Emma Christina; Canavan, Lynn; Pastor-Peidro, Ana; Calvo-Asensio, Irene; Llorens-Agost, Marta; Lowndes, Noel Francis (2013). Atr activates the s-m checkpoint during unperturbed growth to ensure sufficient replication prior to mitotic onset. Cell Reports 5 (4), 1095-1107
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.
Funder
Publisher
Elsevier BV
Publisher DOI
10.1016/j.celrep.2013.10.027
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland