ATM and the epigenetics of the neuronal genome.
ATM and the epigenetics of the neuronal genome.
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DOI：
10.1016/j.mad.2013.05.005
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发表时间：
2013-10
影响因子：
5.3
通讯作者：
Herrup, Karl
中科院分区：
文献类型：
--
作者：
Herrup, Karl
共济失调-毛细血管扩张症（Ataxia-telangiectasia，A-T）是一种由ATM基因突变引起的神经退行性疾病。ATM蛋白是PI 3激酶家族成员，以其在DNA损伤反应中的作用而闻名。虽然DNA损伤的修复是每个CNS神经元必须执行的关键功能，但越来越多的证据表明ATM的全部功能包括一些与DNA损伤无关但对神经元存活和正常功能至关重要的功能。例如，ATM参与突触囊泡运输的调节，并且对于维持正常LTP至关重要。此外，ATM有助于确保HDAC 4的细胞质定位，从而通过抑制全基因组蛋白脱乙酰化来维持神经元基因组的组蛋白“密码”，这改变了许多基因的信息和蛋白质水平，这些基因对神经元的存活和功能很重要。越来越多的ATM功能超出了其在DNA损伤反应中的作用，这为A-T个体表达如此广泛的神经系统症状提供了一个新的视角，并表明并非所有A-T症状都需要在DNA修复过程中理解。
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.
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影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
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DOI：
10.1073/pnas.0611671104
发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.89.4.1194
发表时间：
1992-02-15
影响因子：
11.1
作者：
ALUBAIDI, MR;HOLLYFIELD, JG;BAEHR, W
通讯作者：
BAEHR, W