ATM function and telomere stability.
Accumulation of DNA damage has been associated with the onset of senescence and predisposition to cancer. The gene responsible for ataxia telangiectasia (A-T) is ATM (ataxia-telangiectasia mutant), a master controller of cellular pathways and networks, orchestrating the responses to a specific type of DNA damage: the double strand break. Based on the homology of the human ATM gene to the TEL1, MEC1 and rad3 genes of yeast, it has now been demonstrated that mutations in ATM lead to defective telomere maintenance in mammalian cells. While ATM has both nuclear and cytoplasmic functions, this review will focus on its roles in telomere metabolism and how ATM and telomeres serve as controllers of cellular responses to DNA damage.
Pandita
Tej K
TK
Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York, NY 10032, USA. tpl1@columbia.edu
D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000737:chemistry; D004268:DNA-Binding Proteins; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D016315:Proto-Oncogene Proteins c-abl; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D019098:Telomerase