The impact of aneuploidy on cellular homeostasis

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Genomic instability is a common feature of tumours that has a wide range of disruptive effects on cellular homeostasis. In this review we briefly discuss how instability comes about, then focus on the impact of gain or loss of DNA (aneuploidy) on oxidative stress. We discuss several mechanisms that lead from aneuploidy to the production of reactive oxygen species, including the effects on protein complex stoichiometry, endoplasmic reticulum stress and metabolic disruption. Each of these are involved in positive feedback loops that amplify relatively minor genetic changes into major cellular disruption or cell death, depending on the capacity of the cell to induce antioxidants or processes such as mitophagy that can moderate the disruption. Finally we examine the direct effects of reactive oxygen species on mitosis and how oxidative stress can compromise centrosome number, cytoskeletal integrity and signalling processes that are vital for mitotic fidelity.

Original languageEnglish
Pages (from-to)705-713
Number of pages10
JournalFree Radical Research
Volume53
Issue number7
Early online date2019
DOIs
Publication statusPublished - 7 Jun 2019

Keywords

  • Aneuploidy
  • DNA damage
  • genomic instability
  • metabolism
  • oxidative stress
  • proteotoxic stress
  • reactive oxygen species (ROS)

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