The impact of a negligent G2/M checkpoint on genomic instability and cancer induction

Nat Rev Cancer. 2007 Nov;7(11):861-9. doi: 10.1038/nrc2248.

Abstract

DNA damage responses (DDR) encompass DNA repair and signal transduction pathways that effect cell cycle checkpoint arrest and/or apoptosis. How DDR pathways respond to low levels of DNA damage, including low doses of ionizing radiation, is crucial for assessing environmental cancer risk. It has been assumed that damage-induced cell cycle checkpoints respond to a single double strand break (DSB) but the G2/M checkpoint, which prevents entry into mitosis, has recently been shown to have a defined threshold of 10-20 DSBs. Here, we consider the impact of a negligent G2/M checkpoint on genomic stability and cancer risk.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Cell Division / physiology*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology*
  • DNA / radiation effects
  • DNA Breaks, Double-Stranded
  • DNA Damage*
  • DNA Repair / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • G2 Phase / physiology*
  • Genes, cdc
  • Genomic Instability*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology
  • Models, Biological
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • Risk
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Tumor Suppressor Proteins
  • DNA
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases