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Controlling the topology of mammalianmitochondrial DNA

Lookup NU author(s): Dr Katja Menger, Alejandro Rodriguez Luis, Dr James Chapman, Dr Thomas Nicholls

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

The genome of mitochondria, called mtDNA, is a small circular DNA molecule present at thousands of copies per human cell. MtDNA is packaged into nucleoprotein complexes called nucleoids, and the density of mtDNA packaging affects mitochondrial gene expression. Genetic processes such as transcription, DNA replication and DNA packaging alter DNA topology, and these topological problems are solved by a family of enzymes called topoisomerases. Within mitochondria, topoisomerases are involved firstly in the regulation of mtDNA supercoiling and secondly in disentangling interlinked mtDNA molecules following mtDNA replication. The loss of mitochondrial topoisomerase activity leads to defects in mitochondrial function, and variants in the dual-localized type IA topoisomerase TOP3A have also been reported to cause human mitochondrial disease. We review the current knowledge on processes that alter mtDNA topology, how mtDNA topology is modulated by the action of topoisomerases, and the consequences of altered mtDNA topology for mitochondrial function and human health.


Publication metadata

Author(s): Menger KE, Rodriguez-Luis A, Chapman J, Nicholls TJ

Publication type: Review

Publication status: Published

Journal: Open Biology

Year: 2021

Volume: 11

Issue: 9

Online publication date: 22/09/2021

Acceptance date: 31/08/2021

ISSN (electronic): 2046-2441

URL: https://doi.org/10.1098/rsob.210168

DOI: 10.1098/rsob.210168

PubMed id: 34547213


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