2017
DOI: 10.1016/j.cels.2017.09.015
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Orchestration of DNA Damage Checkpoint Dynamics across the Human Cell Cycle

Abstract: Although molecular mechanisms that prompt cell cycle arrest in response to DNA damage have been elucidated, the systems-level properties of DNA damage checkpoints are not understood. Here, using time-lapse microscopy and simulations that model the cell cycle as a series of Poisson processes, we characterize DNA damage checkpoints in individual, asynchronously proliferating cells. We demonstrate that within early G1 and G2, checkpoints are stringent: DNA damage triggers an abrupt, all-or-none cell cycle arrest.… Show more

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Cited by 146 publications
(134 citation statements)
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“…According to the many‐for‐all model, observation of coupling between cell cycle phases would imply that phase‐controlling factors are relatively more abundant in certain cell types. Third, we employ a more accurate method of measuring cell cycle phase durations based on appearance and disappearance of PCNA foci during S phase and validate these results with an orthogonal measurement of phase duration (Grant et al , ; Appendix Fig S2B and C; Chao et al , ; Grant et al , ). Previous studies employed the FUCCI reporter system to distinguish G1 and S‐G2‐M cells, but this system is known to give unclear cell cycle phase boundaries (Wilson et al , ; Grant et al , ).…”
Section: Discussionmentioning
confidence: 64%
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“…According to the many‐for‐all model, observation of coupling between cell cycle phases would imply that phase‐controlling factors are relatively more abundant in certain cell types. Third, we employ a more accurate method of measuring cell cycle phase durations based on appearance and disappearance of PCNA foci during S phase and validate these results with an orthogonal measurement of phase duration (Grant et al , ; Appendix Fig S2B and C; Chao et al , ; Grant et al , ). Previous studies employed the FUCCI reporter system to distinguish G1 and S‐G2‐M cells, but this system is known to give unclear cell cycle phase boundaries (Wilson et al , ; Grant et al , ).…”
Section: Discussionmentioning
confidence: 64%
“…It has been firmly established in previous studies that, during S phase, PCNA is loaded at DNA replication forks and forms foci in well-described punctate patterns (Madsen & Celis, 1985;Kennedy et al, 2000;Leonhardt, 2000;Wilson et al, 2016;Chao et al, 2017). PCNA localization is precisely correlated with DNA replication and thus is a bona fide marker of S phase (Madsen & Celis, 1985;Leonhardt, 2000;Burgess et al, 2012;Wilson et al, 2016;Chao et al, 2017;Zerjatke et al, 2017). The transition from diffuse to punctate (G1/S) and from punctate back to diffuse (S/G2) was readily detectable between consecutive frames of time-lapse imaging by both manual and automated procedures (Barr et al, 2017;Appendix Fig S2A).…”
Section: Cell Cycle Phase Durations Are Uncoupled Under Unstressed Comentioning
confidence: 76%
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