The ATM-mediated DNA-damage response: taking shape.
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.
Shiloh
Yosef
Y
The David and Inez Myers Laboratory for Genetic Research, Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. yossih@post.tau.ac.il
D017766:Acid Anhydride Hydrolases; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D000076228:MRE11 Homologue Protein; D008954:Models, Biological; D010750:Phosphoproteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000071857:Tumor Suppressor p53-Binding Protein 1; D029867:Xenopus Proteins / Q000502:physiology
D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C121766:MRE11 protein, human; C511600:NBN protein, Xenopus; D010750:Phosphoproteins; C498301:TP53BP1 protein, human; D025521:Tumor Suppressor Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; D029867:Xenopus Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes