Eukaryotic cells activate the S-phase checkpoint signal transduction pathway in response to DNA replication stress. Affected by the noise in biochemical reactions, such activation process demonstrates cell-to-cell variability. Here, through the analysis of microfluidics-integrated time-lapse imaging, we found multiple S-phase checkpoint activations in a certain budding yeast cell cycle. Yeast cells not only varied in their activation moments but also differed in the number of activations within the cell cycle, resulting in a stochastic multiple activation process. By investigating dynamics at the single-cell level, we showed that stochastic waiting times between consecutive activations are exponentially distributed and independent from each other. Finite DNA replication time provides a robust upper time limit to the duration of multiple activations. The mathematical model, together with further experimental evidence from the mutant strain, revealed that the number of activations under different levels of replication stress agreed well with Poisson distribution. Therefore, the activation events of S-phase checkpoint meet the criterion of Poisson process during DNA replication. In sum, the observed Poisson activation process may provide new insights into the complex stochastic dynamics of signal transduction pathways.

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Journal Article

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Gao X, Zhou P, Li F

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