DNA damage-induced apoptosis.
Unicellular organisms respond to the presence of DNA lesions by activating cell cycle checkpoint and repair mechanisms, while multicellular animals have acquired the further option of eliminating damaged cells by triggering apoptosis. Defects in DNA damage-induced apoptosis contribute to tumorigenesis and to the resistance of cancer cells to a variety of therapeutic agents. The intranuclear mechanisms that signal apoptosis after DNA damage overlap with those that initiate cell cycle arrest and DNA repair, and the early events in these pathways are highly conserved. In addition, multiple independent routes have recently been traced by which nuclear DNA damage can be signalled to the mitochondria, tipping the balance in favour of cell death rather than repair and survival. Here, we review current knowledge of nuclear DNA damage signalling, giving particular attention to interactions between these nuclear events and apoptotic processes in other intracellular compartments.
Norbury
Chris J
CJ
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Zhivotovsky
Boris
B
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000502:physiology; D053143:Caspase 2; D020169:Caspases / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D053200:Fas-Associated Death Domain Protein; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D006657:Histones; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D053143:Caspase 2; D020169:Caspases