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CHRONOCRISIS: When Cell Cycle Asynchrony Generates DNA Damage in Polyploid Cells.

Simon Gemble1, Renata Basto1

  • 1Biology of Centrosomes and Genetic Instability Lab, Institut Curie, PSL Research University, CNRS UMR144, 12 rue Lhomond, Paris, 75005, France.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|September 5, 2020
PubMed
Summary

Polyploid cells with multiple chromosome sets can arise from normal development or abnormal cell division. Non-programmed polyploidy may lead to DNA damage and genetic instability, potentially driving cancer progression.

Keywords:
DNA damageasynchronycancercell cyclegenetic instabilitymitosispolyploidy

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Area of Science:

  • Cell Biology
  • Genetics
  • Cancer Research

Background:

  • Polyploid cells possess multiple chromosome sets, arising from either programmed development or non-programmed events.
  • Programmed polyploidy typically occurs during terminal differentiation, limiting cell proliferation.
  • Non-programmed polyploidy can result in proliferating cells, potentially leading to genomic instability and diseases like cancer.

Purpose of the Study:

  • To review mechanisms generating polyploidy.
  • To discuss challenges in polyploid cell division.
  • To highlight how asynchronous nuclear cell cycle progression (chronocrisis) in polyploid cells can induce DNA damage and abnormal karyotypes.

Main Methods:

  • Literature review of polyploidization mechanisms.
  • Discussion of cell cycle progression and DNA damage in polyploid cells.
  • Analysis of a recent study on chronocrisis and its implications.

Main Results:

  • Polyploidization mechanisms are diverse, with programmed and non-programmed pathways having distinct outcomes.
  • Asynchronous cell cycle progression (chronocrisis) in polyploid cells can lead to DNA damage upon mitotic entry.
  • Mitosis in non-programmed polyploid cells may generate abnormal karyotypes and contribute to genetic instability.

Conclusions:

  • Non-programmed polyploidy presents significant challenges for accurate cell division.
  • Chronocrisis is a key mechanism linking polyploidy to DNA damage and potential oncogenesis.
  • Understanding these mechanisms is crucial for cancer research and therapeutic strategies.