The termini of DNA strand breaks induced by reactive oxygen species or by abortive DNA metabolic intermediates require processing to enable subsequent gap filling and ligation to proceed. The three proteins, tyrosyl DNA-phosphodiesterase 1 (TDP1), aprataxin (APTX) and polynucleotide kinase/phosphatase (PNKP) each act on a discrete set of modified strand-break termini. Recently, a series of neurodegenerative and neurodevelopmental disorders have been associated with mutations in the genes coding for these proteins. Mutations in TDP1 and APTX have been linked to Spinocerebellar ataxia with axonal neuropathy (SCAN1) and Ataxia-ocular motor apraxia 1 (AOA1), respectively, while mutations in PNKP are considered to be responsible for Microcephaly with seizures (MCSZ) and Ataxia-ocular motor apraxia 4 (AOA4). Here we present an overview of the mechanisms of these proteins and how their impairment may give rise to their respective disorders.

中文翻译：

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与DNA链断裂加工酶相关的神经系统疾病。

由活性氧或流产的DNA代谢中间体诱导的DNA链断裂末端需要进行处理，以确保后续的缺口填充和连接能够进行。酪氨酸DNA-磷酸二酯酶1（TDP1），紫杉醇（APTX）和多核苷酸激酶/磷酸酶（PNKP）这三种蛋白各自作用于一组离散的修饰的链断裂末端。最近，一系列神经退行性疾病和神经发育障碍已与编码这些蛋白质的基因突变相关。TDP1和APTX的突变已分别与轴突性神经病（SCAN1）和共济失调-眼运动失用症1（AOA1）相关联，而PNKP中的突变被认为是引起小头性癫痫发作（MCSZ）和共济失调-眼的原因运动性失用症4（AOA4）。