TOP3A (Topoisomerase 3a) decatenates mitochondrial DNA

Stable Identifier
R-HSA-9914922
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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After replication of the H strand and L strand, the two daughter double-stranded molecules remain catenated at the H strand origin (OriH) by a single strand of DNA and are then separated by Topoisomerase 3A (TOP3A) (Nicholls et al. 2018, Erdinc et al. 2023, reviewed in Nicholls and Gustafsson 2018), a type I topoisomerase (Yang et al. 2010). TOP3A localizes to both the nucleus and mitochondria (Wang et al. 2002). Specific mutants of TOP3A exhibit decreased decatenation activity and are associated with mitochondrial dysfunction (Erdinc et al. 2023).
Literature References
PubMed ID Title Journal Year
20445207 Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1

Yang, J, Bachrati, CZ, Ou, J, Hickson, ID, Brown, GW

J Biol Chem 2010
37013609 Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability

Erdinc, D, Rodríguez-Luis, A, Fassad, MR, Mackenzie, S, Watson, CM, Valenzuela, S, Xie, X, Menger, KE, Sergeant, K, Craig, K, Hopton, S, Falkous, G, Poulton, J, Garcia-Moreno, H, Giunti, P, de Moura Aschoff, CA, Morales Saute, JA, Kirby, AJ, Toro, C, Wolfe, L, Novacic, D, Greenbaum, L, Eliyahu, A, Barel, O, Anikster, Y, McFarland, R, Gorman, GS, Schaefer, AM, Gustafsson, CM, Taylor, RW, Falkenberg, M, Nicholls, TJ

EMBO Mol Med 2023
29290614 Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA

Nicholls, TJ, Nadalutti, CA, Motori, E, Sommerville, EW, Gorman, GS, Basu, S, Hoberg, E, Turnbull, DM, Chinnery, PF, Larsson, NG, Larsson, E, Falkenberg, M, Taylor, RW, Griffith, JD, Gustafsson, CM

Mol Cell 2018
Participants
Participates
Catalyst Activity

DNA topoisomerase type I (single strand cut, ATP-independent) activity of TOP3A:Mg2+ [mitochondrial matrix]

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