Abstract

Cell cycle progression is carefully coordinated with a cell’s intra- and extracellular environment. While some pathways have been identified that communicate information from the environment to the cell cycle, a systematic understanding of how this information is dynamically processed is lacking. We address this by performing dynamic sensitivity analysis of three mathematical models of the cell cycle in Saccharomyces cerevisiae. We demonstrate that these models make broadly consistent qualitative predictions about cell cycle progression under dynamically changing conditions. For example, it is shown that the models predict anticorrelated changes in cell size and cell cycle duration under different environments independently of the growth rate. This prediction is validated by comparison to available literature data. Other consistent patterns emerge, such as widespread nonmonotonic changes in cell size down generations in response to parameter changes. We extend our analysis by investigating glucose signalling to the cell cycle, showing that known regulation of Cln3 translation and Cln1,2 transcription by glucose is sufficient to explain the experimentally observed changes in cell cycle dynamics at different glucose concentrations. Together, these results provide a framework for understanding the complex responses the cell cycle is capable of producing in response to dynamic environments.

Highlights

  • The cell cycle is the process by which cells alternate replication of their DNA with cell division

  • While some pathways have been identified that communicate information from the environment to the cell cycle, a systematic understanding of how this information is dynamically processed is lacking. We address this by performing dynamic sensitivity analysis of three mathematical models of the cell cycle in Saccharomyces cerevisiae

  • We demonstrate that these models make broadly consistent qualitative predictions about cell cycle progression under dynamically changing conditions

Read more

Summary

Introduction

The cell cycle is the process by which cells alternate replication of their DNA with cell division. As a central process in the life of a cell, it is subject to multiple forms of regulation. These range from hormonal and growth factor signals in higher organisms, down to nutrient and stress signals in micro-organisms. While there has been much progress in understanding the mechanisms driving cell cycle progression, a system-level understanding of how signals regulate this progression has been lacking. We investigate the dynamic response of the cell cycle to perturbations. We apply a combination of computational and mathematical analyses to study how the cell cycle of a particular model organism—the budding yeast Saccharomyces cerevisiae—responds to changes in conditions

Results
Discussion
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.