ATM and related protein kinases: safeguarding genome integrity.
Maintenance of genome stability is essential for avoiding the passage to neoplasia. The DNA-damage response--a cornerstone of genome stability--occurs by a swift transduction of the DNA-damage signal to many cellular pathways. A prime example is the cellular response to DNA double-strand breaks, which activate the ATM protein kinase that, in turn, modulates numerous signalling pathways. ATM mutations lead to the cancer-predisposing genetic disorder ataxia-telangiectasia (A-T). Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.
Shiloh
Yosef
Y
The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. yossih@post.tau.ac.il
D000818:Animals; D001260:Ataxia Telangiectasia / Q000201:enzymology / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019457:Chromosome Breakage; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D018816:Genes, cdc; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D005810:Multigene Family; D009386:Neoplastic Syndromes, Hereditary / Q000201:enzymology / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576325:Atm protein, mouse