Defying death after DNA damage

Nature. 2000 Oct 12;407(6805):777-83. doi: 10.1038/35037717.

Abstract

DNA damage frequently triggers death by apoptosis. The irreversible decision to die can be facilitated or forestalled through integration of a wide variety of stimuli from within and around the cell. Here we address some fundamental questions that arise from this model. Why should DNA damage initiate apoptosis in the first place? In damaged cells, what are the alternatives to death and why should they be selected in some circumstances but not others? What signals register DNA damage and how do they impinge on the effector pathways of apoptosis? Is there a suborganellar apoptosome complex effecting the integration of death signals within the nucleus, just as there is in the cytoplasm? And what are the consequences of failure to initiate apoptosis in response to DNA damage?

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Ataxia Telangiectasia Mutated Proteins
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • DNA Damage*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • Forecasting
  • Humans
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins c-abl / physiology
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / physiology
  • Tumor Suppressor Protein p53 / physiology
  • Tumor Suppressor Proteins

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins c-abl
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases