The impact of a negligent G2/M checkpoint on genomic instability and cancer induction.
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.
Löbrich
Markus
M
Darmstadt University of Technology, Radiation Biology and DNA Repair, 64287 Darmstadt, Germany. lobrich@bio.tu-darmstadt.de
Jeggo
Penny A
PA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016195:G2 Phase / Q000502:physiology*; D018816:Genes, cdc; D042822:Genomic Instability; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008954:Models, Biological; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012306:Risk; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases