Atr activates the s-m checkpoint during unperturbed growth to ensure sufficient replication prior to mitotic onset
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2013-11-01Author
Eykelenboom, John Kenneth
Harte, Emma Christina
Canavan, Lynn
Pastor-Peidro, Ana
Calvo-Asensio, Irene
Llorens-Agost, Marta
Lowndes, Noel Francis
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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
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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.