Increased negative supercoiling of mtDNA in TOP1mt knockout mice and presence of topoisomerases IIα and IIβ in vertebrate mitochondria.
Bottom Line: Topoisomerases are critical for replication, DNA packing and repair, as well as for transcription by allowing changes in DNA topology.This finding suggested imbalanced topoisomerase activity in the absence of Top1mt and the activity of other topoisomerases in mitochondria.The presence of Top2α-DNA complexes in the mtDNA D-loop region, at the sites where both ends of 7S DNA are positioned, suggests a structural role for Top2 in addition to its classical topoisomerase activities.
Affiliation: Laboratory of Molecular Pharmacology and Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA firstname.lastname@example.org.Show MeSH
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Mentions: To detect Top2 activity in mitochondria, we took advantage of the fact that type II topoisomerases cleave the DNA backbone by covalent attachment to the 5′-ends of the break, and that these transient catalytic intermediates, which are referred to as cleavage complexes (2,3) can be trapped by etoposide, a selective Top2α–Top2β poison widely used for cancer treatment (3,35,36). Consistent with the presence of Top2α and Top2β in mitochondria, treatment of purified mitochondria from MCF-7 cells with etoposide generated Top2-DNA complexes, as measured by the ICE bioassay (22,23) (Figure 5A).
Affiliation: Laboratory of Molecular Pharmacology and Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA email@example.com.