title: ATM and the epigenetics of the neuronal genome.
abstract: Ataxia-telangiectasia (A-T) is a neurodegenerative syndrome caused by the mutation of the ATM gene. The ATM protein is a PI3kinase family member best known for its role in the DNA damage response. While repair of DNA damage is a critical function that every CNS neuron must perform, a growing body of evidence indicates that the full range of ATM functions includes some that are unrelated to DNA damage yet are essential to neuronal survival and normal function. For example, ATM participates in the regulation of synaptic vesicle trafficking and is essential for the maintenance of normal LTP. In addition ATM helps to ensure the cytoplasmic localization of HDAC4 and thus maintains the histone 'code' of the neuronal genome by suppressing genome-wide histone deacetylation, which alters the message and protein levels of many genes that are important for neuronal survival and function. The growing list of ATM functions that go beyond its role in the DNA damage response offers a new perspective on why individuals with A-T express such a wide range of neurological symptoms, and suggests that not all A-T symptoms need to be understood in the context of the DNA repair process.
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, United States; Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong. Electronic address: Herrup@Biology.Rutgers.Edu.
authors.forename: Karl
authors.initials: K
authors.lastname: Herrup
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006655:Histone Deacetylases / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012097:Repressor Proteins / Q000276:immunology / Q000378:metabolism; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D012097:Repressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C400300:HDAC4 protein, human; D006655:Histone Deacetylases
keywords: Cell cycle; Histone deacetylase; LTP; Neurodegeneration; Synaptic vesicle