Evidence that the human cell cycle is a series of uncoupled, memoryless phases
Abstract 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...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2019-03-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20188604 |
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| _version_ | 1849389062773800960 |
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| author | Hui Xiao Chao Randy I Fakhreddin Hristo K Shimerov Katarzyna M Kedziora Rashmi J Kumar Joanna Perez Juanita C Limas Gavin D Grant Jeanette Gowen Cook Gaorav P Gupta Jeremy E Purvis |
| author_facet | Hui Xiao Chao Randy I Fakhreddin Hristo K Shimerov Katarzyna M Kedziora Rashmi J Kumar Joanna Perez Juanita C Limas Gavin D Grant Jeanette Gowen Cook Gaorav P Gupta Jeremy E Purvis |
| author_sort | Hui Xiao Chao |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-81290e9fcfee4492b0f34caf81dfef6d |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2019-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-81290e9fcfee4492b0f34caf81dfef6d2025-08-20T03:42:04ZengSpringer NatureMolecular Systems Biology1744-42922019-03-0115311910.15252/msb.20188604Evidence that the human cell cycle is a series of uncoupled, memoryless phasesHui Xiao Chao0Randy I Fakhreddin1Hristo K Shimerov2Katarzyna M Kedziora3Rashmi J Kumar4Joanna Perez5Juanita C Limas6Gavin D Grant7Jeanette Gowen Cook8Gaorav P Gupta9Jeremy E Purvis10Department of Genetics, University of North Carolina at Chapel HillDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel HillDepartment of Pharmacology, University of North Carolina at Chapel HillDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel HillDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel HillLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillDepartment of Genetics, University of North Carolina at Chapel HillAbstract 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.https://doi.org/10.15252/msb.20188604cell cyclecell‐to‐cell variabilitycomputational systems biologyErlang modelsingle‐cell dynamics |
| spellingShingle | Hui Xiao Chao Randy I Fakhreddin Hristo K Shimerov Katarzyna M Kedziora Rashmi J Kumar Joanna Perez Juanita C Limas Gavin D Grant Jeanette Gowen Cook Gaorav P Gupta Jeremy E Purvis Evidence that the human cell cycle is a series of uncoupled, memoryless phases Molecular Systems Biology cell cycle cell‐to‐cell variability computational systems biology Erlang model single‐cell dynamics |
| title | Evidence that the human cell cycle is a series of uncoupled, memoryless phases |
| title_full | Evidence that the human cell cycle is a series of uncoupled, memoryless phases |
| title_fullStr | Evidence that the human cell cycle is a series of uncoupled, memoryless phases |
| title_full_unstemmed | Evidence that the human cell cycle is a series of uncoupled, memoryless phases |
| title_short | Evidence that the human cell cycle is a series of uncoupled, memoryless phases |
| title_sort | evidence that the human cell cycle is a series of uncoupled memoryless phases |
| topic | cell cycle cell‐to‐cell variability computational systems biology Erlang model single‐cell dynamics |
| url | https://doi.org/10.15252/msb.20188604 |
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