The ATM-mediated DNA-damage response: taking shape

Trends Biochem Sci. 2006 Jul;31(7):402-10. doi: 10.1016/j.tibs.2006.05.004. Epub 2006 Jun 13.

Abstract

Cellular responses to DNA damage are crucial for maintaining homeostasis and preventing the development of cancer. Our understanding of the DNA-damage response has evolved: whereas previously the focus was on DNA repair, we now appreciate that the response to DNA lesions involves a complex, highly branched signaling network. Defects in this response lead to severely debilitating, cancer-predisposing "genomic instability syndromes". Double strand breaks (DSBs) in DNA are potent triggers of the DNA-damage response, which is why they are used to study this pathway. The chief transducer of the DSB signal is the nuclear protein kinase ataxia-telangiectasia mutated (ATM). Genetic, biochemical and structural studies have recently provided insights into the ATM-mediated DSB response, reshaping our view of this signaling pathway while raising new questions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases
  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / physiology*
  • Cyclic AMP Response Element-Binding Protein / physiology
  • DNA Damage / physiology*
  • DNA Repair
  • DNA Repair Enzymes / physiology
  • DNA-Binding Proteins / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology
  • MRE11 Homologue Protein
  • Models, Biological
  • Phosphoproteins / physiology
  • Protein-Serine-Threonine Kinases / physiology*
  • Tumor Suppressor Proteins / physiology*
  • Tumor Suppressor p53-Binding Protein 1
  • Xenopus Proteins / physiology

Substances

  • Cell Cycle Proteins
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • MRE11 protein, human
  • NBN protein, Xenopus
  • Phosphoproteins
  • TP53BP1 protein, human
  • Tumor Suppressor Proteins
  • Tumor Suppressor p53-Binding Protein 1
  • Xenopus Proteins
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • MRE11 Homologue Protein
  • Acid Anhydride Hydrolases
  • Rad50 protein, human
  • DNA Repair Enzymes