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Organization of DNA in Mammalian Mitochondria
Review

Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
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Int. J. Mol. Sci. 2019, 20(12), 3015; https://doi.org/10.3390/ijms20123015
Received: 18 May 2019 / Revised: 14 June 2019 / Accepted: 18 June 2019 / Published: 20 June 2019
Mammalian mitochondria contain four topoisomerases encoded in the nuclear genome: TOP1MT, TOP2α, TOP2β, and TOP3α. They also contain the two known tyrosyl-DNA phosphodiesterases (TDPs): TDP1 and TDP2, including a specific TDP2S isoform. Both TDP1 and TDP2 excise abortive topoisomerase cleavage complexes (TOPccs), yet their molecular structures and mechanisms are different. TDP1 is present across eukaryotes, from yeasts to humans and belongs to the phospholipase D family. It functions without a metal cofactor and has a broad activity range, as it also serves to cleanse blocking 3′-DNA ends bearing phosphoglycolate, deoxyribose phosphate, nucleoside, nucleoside analogs (zidovudine), abasic moieties, and with a lower efficiency, TOP2ccs. Found in higher vertebrates, TDP2 is absent in yeast where TDP1 appears to perform its functions. TDP2 belongs to the exonuclease/endonuclease/phosphodiesterase family and requires magnesium as a cofactor to excise TOP2ccs, and it also excises TOP1ccs, albeit with a lower efficiency. Here, we review TDP1 and TDP2 in the context of mitochondrial DNA repair and discuss potential new research areas centered on the mitochondrial TDPs. View Full-Text
Keywords: mitochondrial DNA; topoisomerases; TDP1; TDP2; ROS; SCAN1; neurological disorders; cancer; antibiotics and antiviral agents mitochondrial DNA; topoisomerases; TDP1; TDP2; ROS; SCAN1; neurological disorders; cancer; antibiotics and antiviral agents
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MDPI and ACS Style

Huang, S.-y.N.; Pommier, Y. Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair. Int. J. Mol. Sci. 2019, 20, 3015. https://doi.org/10.3390/ijms20123015

AMA Style

Huang S-yN, Pommier Y. Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair. International Journal of Molecular Sciences. 2019; 20(12):3015. https://doi.org/10.3390/ijms20123015

Chicago/Turabian Style

Huang, Shar-yin N., and Yves Pommier. 2019. "Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair" International Journal of Molecular Sciences 20, no. 12: 3015. https://doi.org/10.3390/ijms20123015

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