期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 161, 期 -, 页码 130-140出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2016.07.009
关键词
Tyrosyl DNA-phosphodiesterase 1; DNA repair; Aprataxin; DNA strand breaks; Polynucleotide kinase/phosphatase; Neurodegeneration
资金
- Noujaim Graduate Studentship - Alberta Cancer Foundation
- Canadian Cancer Society/Canadian Breast Cancer Research Alliance
- Canadian Institutes of Health Research [CIHR114975]
- National Institutes of Health [CA92584]
- CIHR [MOP 15385]
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 TDPI and APTX have been linked to Spinocerebellar ataxia with axonal neuropathy (SCAN1) and Ataxia-ocular motor apraxia I (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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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