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. The duration of this arrest correlates with the severity of DNA damage. After the cell passes commitment points within G1 and G2, checkpoint stringency is relaxed. By contrast, all of S phase is comparatively insensitive to DNA damage. This checkpoint is graded: instead of halting the cell cycle, increasing DNA damage leads to slower S phase progression. In sum, we show that a cell's response to DNA damage depends on its exact cell-cycle position and that checkpoints are phase-dependent, stringent or relaxed, and graded or all-or-none.
journal_name
Cell Systjournal_title
Cell systemsauthors
Chao HX,Poovey CE,Privette AA,Grant GD,Chao HY,Cook JG,Purvis JEdoi
10.1016/j.cels.2017.09.015subject
Has Abstractpub_date
2017-11-22 00:00:00pages
445-459.e5issue
5eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30436-2journal_volume
5pub_type
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