期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 32, 页码 21446-21457出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.016600
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资金
- National Institutes of Health [GM31819]
- Academy of Finland
- Sigrid Juselius Foundation
- Tampere University Hospital Medical Research Fund
- Universities of Tampere and Helsinki
- Yrjo Jahnsson Foundation
- Elli and Elvi Oksanen Fund of the Pirkanmaa Fund
- Finnish Cultural Foundation
- Finnish Foundation for Cardiovascular Research
- Helsinki Biomedical Graduate School
- European Union
- United Kingdom Medical Research Council
- MRC [MC_U105663140] Funding Source: UKRI
- Medical Research Council [MC_U105663140] Funding Source: researchfish
Analysis of human heart mitochondrial DNA (mtDNA) by electron microscopy and agarose gel electrophoresis revealed a complete absence of the theta-type replication intermediates seen abundantly in mtDNA from all other tissues. Instead only Y- and X-junctional forms were detected after restriction digestion. Uncut heart mtDNA was organized in tangled complexes of up to 20 or more genome equivalents, which could be resolved to genomic monomers, dimers, and linear fragments by treatment with the decatenating enzyme topoisomerase IV plus the cruciform-cutting T7 endonuclease I. Human and mouse brain also contained a population of such mtDNA forms, which were absent, however, from mouse, rabbit, or pig heart. Overexpression in transgenic mice of two proteins involved in mtDNA replication, namely human mitochondrial transcription factor A or the mouse Twinkle DNA helicase, generated abundant four-way junctions in mtDNA of heart, brain, and skeletal muscle. The organization of mtDNA of human heart as well as of mouse and human brain in complex junctional networks replicating via a presumed non-theta mechanism is unprecedented in mammals.
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