4.5 Article

Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease

期刊

MECHANISMS OF AGEING AND DEVELOPMENT
卷 161, 期 -, 页码 121-129

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2016.04.009

关键词

Neurodegeneration; Microcephaly; DNA repair; DNA damage signaling; Polynucleotide kinase phosphatase; Neurologic disease; Single strand break repair; Base excision repair

资金

  1. NIH [NS-37956, CA-21765]
  2. CCSG [P30CA21765]
  3. American Lebanese and Syrian Associated Charities of St. Jude Children's Research Hospital

向作者/读者索取更多资源

A variety of human neurologic diseases are caused by inherited defects in DNA repair. In many cases, these syndromes almost exclusively impact the nervous system, underscoring the critical requirement for genome stability in this tissue. A striking example of this is defective enzymatic activity of polynucleotide kinase-phosphatase (PNKP), leading to microcephaly or neurodegeneration. Notably, the broad neural impact of mutations in PNKP can result in markedly different disease entities, even when the inherited mutation is the same. For example microcephaly with seizures (MCSZ) results from various hypomorphic PNKP mutations, as does ataxia with oculomotor apraxia 4 (AOA4). Thus, other contributing factors influence the neural phenotype when PNKP is disabled. Here we consider the role for PNKP in maintaining brain function and how perturbation in its activity can account for the varied pathology of neurodegeneration or microcephaly present in MCSZ and AOA4 respectively. (C) 2016 Published by Elsevier Ireland Ltd.

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