DNA Damage Checkpoints: From Initiation to Recovery or Adaptation

Curr Opin Cell Biol. 2007 Apr;19(2):238-45. doi: 10.1016/j.ceb.2007.02.009. Epub 2007 Feb 15.

Abstract

In response to diverse genotoxic stresses, cells activate DNA damage checkpoint pathways to protect genomic integrity and promote survival of the organism. Depending on DNA lesions and context, damaged cells with alarmed checkpoints can be eliminated by apoptosis or silenced by cellular senescence, or can survive and resume cell cycle progression upon checkpoint termination. Over the past two years a plethora of mechanistic studies have provided exciting insights into the biology and pathology of checkpoint initiation and signal propagation, and have revealed the various ways in which the response can be terminated: through recovery, adaptation or cancer-prone subversion. Such studies highlight the dynamic nature of these processes and help us to better understand the molecular basis, spatiotemporal orchestration and biological significance of the DNA damage response in normal and cancerous cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / metabolism
  • DNA Damage*
  • DNA Repair*
  • DNA Replication
  • Genes, cdc
  • Genomic Instability
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Signal Transduction

Substances

  • Cell Cycle Proteins