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Publication : Increased negative supercoiling of mtDNA in TOP1mt knockout mice and presence of topoisomerases IIα and IIβ in vertebrate mitochondria.

First Author  Zhang H Year  2014
Journal  Nucleic Acids Res Volume  42
Issue  11 Pages  7259-67
PubMed ID  24803675 Mgi Jnum  J:236443
Mgi Id  MGI:5806119 Doi  10.1093/nar/gku384
Citation  Zhang H, et al. (2014) Increased negative supercoiling of mtDNA in TOP1mt knockout mice and presence of topoisomerases IIalpha and IIbeta in vertebrate mitochondria. Nucleic Acids Res 42(11):7259-67
abstractText  Topoisomerases are critical for replication, DNA packing and repair, as well as for transcription by allowing changes in DNA topology. Cellular DNA is present both in nuclei and mitochondria, and mitochondrial topoisomerase I (Top1mt) is the only DNA topoisomerase specific for mitochondria in vertebrates. Here, we report in detail the generation of TOP1mt knockout mice, and demonstrate that mitochondrial DNA (mtDNA) displays increased negative supercoiling in TOP1mt knockout cells and murine tissues. This finding suggested imbalanced topoisomerase activity in the absence of Top1mt and the activity of other topoisomerases in mitochondria. Accordingly, we found that both Top2alpha and Top2beta are present and active in mouse and human mitochondria. The presence of Top2alpha-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.
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