title: ATM protein kinase: the linchpin of cellular defenses to stress.
abstract: ATM is the most significant molecule involved in monitoring the genomic integrity of the cell. Any damage done to DNA relentlessly challenges the cellular machinery involved in recognition, processing and repair of these insults. ATM kinase is activated early to detect and signal lesions in DNA, arrest the cell cycle, establish DNA repair signaling and faithfully restore the damaged chromatin. ATM activation plays an important role as a barrier to tumorigenesis, metabolic syndrome and neurodegeneration. Therefore, studies of ATM-dependent DNA damage signaling pathways hold promise for treatment of a variety of debilitating diseases through the development of new therapeutics capable of modulating cellular responses to stress. In this review, we have tried to untangle the complex web of ATM signaling pathways with the purpose of pinpointing multiple roles of ATM underlying the complex phenotypes observed in AT patients.
authors.affiliation: Institute of Molecular Biology and Biotechnology, The University of Lahore, 1 Km Raiwind Road, Thokar Niaz Baig, Lahore, Pakistan.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Bhatti
authors.forename: Sergei
authors.initials: S
authors.lastname: Kozlov
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.forename: Ali
authors.initials: A
authors.lastname: Naqi
authors.forename: Martin
authors.initials: M
authors.lastname: Lavin
authors.forename: Kum Kum
authors.initials: KK
authors.lastname: Khanna
mesh_terms: D017766:Acid Anhydride Hydrolases; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000503:physiopathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D000076228:MRE11 Homologue Protein; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D046912:Multiprotein Complexes; C112156:NBN protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM 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