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[Genetic control of cell proliferation and the evolution of the cell cycle]
Abstract:
The characteristics of temperature-sensitive cell cycle mutants along with cell fusion studies suggest that gene-dependent synthesis of the inducers of DNA replication is submitted to negative control via an endogenous inhibitor. The dependence of metazoan cell proliferation on extracellular stimulators (hormones, serum factors etc.) appears to be determined by these inhibitors. By contrast, prokaryotic cells and eukaryotic unicellular organisms seem to synthesize the inducers of DNA replication constitutively which enables these cells to proliferate with no specific stimulators. Thus, the following types of the cell cycle may exist in living organisms: A--prokaryotic type of cell cycle where DNA can be synthesized continuously under conditions of nutrient abundance; B--primitive eukaryotic type where DNA replication is interrupted by the condensation of chromosomes prior to mitosis; C--metazoan eukaryotic cell cycle of a higher order where cells after mitosis pass into a resting state, under the influence of endogenous inhibitors and resume the proliferation in a stochastic manner under the effect of exogenous activators. The alternation of active proliferation and resting in the cell life cycle is a necessary prerequisite for cell specialization and population-size control. The essential feature of evolutionary cell cycle reorganization is a substitution of the unlimited primitive cell multiplication with eukaryotic organization of genome and specific cell functions in the multicellular organism.
Insights
Cell proliferation is regulated by internal inhibitors and external factors. Different cell types, from prokaryotes to metazoans, exhibit distinct cell cycle control mechanisms influencing specialization and population size.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Context:
- Cell cycle regulation is fundamental to organism development and function.
- Understanding the control of DNA replication is key to cell proliferation.
- Metazoan cell proliferation relies on external signals, unlike simpler organisms.
Purpose:
- To investigate the regulatory mechanisms controlling DNA replication and cell cycle progression.
- To differentiate between prokaryotic, primitive eukaryotic, and metazoan eukaryotic cell cycle types.
- To elucidate the role of endogenous inhibitors and exogenous activators in cell proliferation.
Summary:
- Gene-dependent synthesis of DNA replication inducers is negatively controlled by endogenous inhibitors.
- Prokaryotic and unicellular eukaryotes constitutively synthesize replication inducers, enabling proliferation without specific stimulators.
- Metazoan cells exhibit a higher-order cell cycle with resting states regulated by inhibitors and activators, facilitating specialization and population control.
Impact:
- Proposes a classification of cell cycle types based on regulatory mechanisms.
- Highlights the evolutionary shift from primitive cell multiplication to complex eukaryotic cell cycles.
- Explains the necessity of cell cycle alternation for cell specialization and multicellular organism organization.