The role of ATM and ATR in DNA damage-induced cell cycle control

Prog Cell Cycle Res. 2003;5:393-411.

Abstract

Ataxia-Telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are members of the phosphatidyl inositol 3-kinase-like family of serine/threonine protein kinases (PIKKs), and play important roles in the cellular response to DNA damage. Activation of ATM by ionizing radiation results in the activation of signal transduction pathways that induce cell cycle arrest at G1/S, S and G2/M. ATR is required for cell cycle arrest in response to DNA-damaging agents such as ultraviolet radiation that cause bulky lesions. This review focuses on the role of ATM and ATR in various DNA damage response pathways, and discusses the potential for targeting these pathways for the development of novel therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle / drug effects
  • Cell Cycle / genetics*
  • Cell Cycle / radiation effects
  • Cell Cycle Proteins*
  • DNA Damage / genetics*
  • DNA Damage / radiation effects
  • DNA-Binding Proteins
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Genes, cdc / drug effects
  • Genes, cdc / physiology*
  • Genes, cdc / radiation effects
  • Humans
  • Protein-Serine-Threonine Kinases / drug effects
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / radiation effects
  • Radiation, Ionizing
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Tumor Suppressor Proteins
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases