Topoisomerase-Mediated DNA Damage in Neurological Disorders.

Topoisomerase-Mediated DNA Damage in Neurological Disorders.
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DOI:
10.3389/fnagi.2021.751742
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发表时间:
2021
影响因子:
4.8
通讯作者:
Madabhushi R
Madabhushi R
中科院分区:
医学2区
文献类型:
--
作者:
Crewe M;Madabhushi R

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神经系统易受基因组不稳定和DNA损伤反应因子突变的影响,导致许多发育性和进行性神经系统疾病。尽管如此,与神经元功能障碍发展最相关的DNA损伤的来源和机制尚不清楚。TDP1和TDP2突变患者主要神经异常的鉴定表明,拓扑异构酶介导的DNA损伤可能是神经元功能障碍的重要潜在来源。在这里,我们回顾了拓扑异构酶诱导的神经元DNA损伤的潜在来源,描述了已经进化到修复这种损伤的细胞机制,并讨论了这些修复机制对预防神经系统疾病的重要性。
The nervous system is vulnerable to genomic instability and mutations in DNA damage response factors lead to numerous developmental and progressive neurological disorders. Despite this, the sources and mechanisms of DNA damage that are most relevant to the development of neuronal dysfunction are poorly understood. The identification of primarily neurological abnormalities in patients with mutations in TDP1 and TDP2 suggest that topoisomerase-mediated DNA damage could be an important underlying source of neuronal dysfunction. Here we review the potential sources of topoisomerase-induced DNA damage in neurons, describe the cellular mechanisms that have evolved to repair such damage, and discuss the importance of these repair mechanisms for preventing neurological disorders.
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