Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mech Ageing Dev. 2013 Oct;134(10):434-9. doi: 10.1016/j.mad.2013.05.005. Epub 2013 May 23.

ATM and the epigenetics of the neuronal genome.

Author information

  • 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.

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.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

Cell cycle; Histone deacetylase; LTP; Neurodegeneration; Synaptic vesicle

PMID:
23707635
[PubMed - indexed for MEDLINE]
PMCID:
PMC3791148
[Available on 2014/10/1]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk