The two edges of the ATM sword: co-operation between repair and checkpoint functions.
ATM is a central component of a signal transduction process that responds to DNA double strand breaks (DSBs) ultimately effecting cell cycle checkpoint arrest and/or apoptosis. Recent studies have shown that ATM also regulates a mechanism of processing a subset of DNA ends that appear to be difficult to ligate, since they are rejoined with slow kinetics in control cells. In the absence of this process, which involves the nuclease, Artemis, the DSBs either remain unrejoined or potentially undergo misrejoining. Thus, ATM's checkpoint function specifically facilitates its repair function. Here, we discuss the contribution of this novel function of ATM to survival after ionising irradiation and to cancer avoidance. We suggest that ATM's strength as a damage response protein lies in the co-ordination of its repair and checkpoint functions making a razor sharp knife out of two blunter edges.
Löbrich
Markus
M
Fachrichtung Biophysik, Universität des Saarlandes, Homburg/Saar, Germany. p.a.jeggo@sussex.ac.uk
Jeggo
Penny A
PA
D000818:Animals; D001260:Ataxia Telangiectasia / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004720:Endonucleases; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011836:Radiation Tolerance; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C426344:DCLRE1C protein, human; D004720:Endonucleases