Evidence that the human cell cycle is a series of uncoupled, memoryless phases
| Autor: | Jeremy E. Purvis, Gaorav P. Gupta, Rashmi Kumar, Hristo K Shimerov, Hui Xiao Chao, Juanita C. Limas, Randy I Fakhreddin, Gavin D. Grant, Katarzyna M. Kedziora, Joanna Perez, Jeanette Gowen Cook |
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| Rok vydání: | 2019 |
| Předmět: |
DNA damage
Phase (waves) Biology Models Biological Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine computational systems biology Humans Quantitative Biology & Dynamical Systems 030304 developmental biology Cyclin 0303 health sciences single‐cell dynamics General Immunology and Microbiology DNA synthesis Series (mathematics) Kinase Applied Mathematics Cell Cycle Cyclin-dependent kinase 2 Articles Erlang model Cell cycle cell‐to‐cell variability Computational Theory and Mathematics Biophysics biology.protein General Agricultural and Biological Sciences 030217 neurology & neurosurgery Information Systems |
| Zdroj: | Molecular Systems Biology |
| ISSN: | 1744-4292 |
| DOI: | 10.15252/msb.20188604 |
| Popis: | The cell cycle is canonically described as a series of four consecutive phases: G1, S, G2, and M. In single cells, the duration of each phase varies, but the quantitative laws that govern phase durations are not well understood. Using time‐lapse microscopy, we found that each phase duration follows an Erlang distribution and is statistically independent from other phases. We challenged this observation by perturbing phase durations through oncogene activation, inhibition of DNA synthesis, reduced temperature, and DNA damage. Despite large changes in durations in cell populations, phase durations remained uncoupled in individual cells. These results suggested that the independence of phase durations may arise from a large number of molecular factors that each exerts a minor influence on the rate of cell cycle progression. We tested this model by experimentally forcing phase coupling through inhibition of cyclin‐dependent kinase 2 (CDK2) or overexpression of cyclin D. Our work provides an explanation for the historical observation that phase durations are both inherited and independent and suggests how cell cycle progression may be altered in disease states. |
| Databáze: | OpenAIRE |
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