Prominent mitochondrial DNA recombination intermediates in human heart muscle.

TitleProminent mitochondrial DNA recombination intermediates in human heart muscle.
Publication TypeJournal Article
Year of Publication2001
AuthorsKajander, OA, Karhunen, PJ, Holt, IJ, Jacobs, HT
JournalEMBO Rep
Volume2
Issue11
Pagination1007-12
Date Published2001 Nov
ISSN1469-221X
KeywordsBlotting, Southern, DNA, DNA Repair, DNA, Mitochondrial, Electrophoresis, Agar Gel, Humans, Muscle, Skeletal, Myocardium, Placenta, Recombination, Genetic
Abstract

Recombination intermediates containing four-way (Holliday) junctions are generated during DNA repair and replication in many systems, including yeast mitochondrial DNA (mtDNA). In contrast, convincing evidence for recombination in mammalian mtDNA is lacking. We have used two-dimensional agarose-gel electrophoresis to analyse non-linear forms of mtDNA in human heart muscle. Replication intermediates from both the coupled and strand-asynchronous mtDNA replication pathways were detected. An additional class of non-linear molecules, with the electrophoretic properties of four-way junctions, was also prominent. These molecules were insensitive to topoisomerase I or RNase H, but were diminished by branch migration or RuvC treatment. Junctional molecules were detected in all regions of the mitochondrial genome, were found in myocardial DNA from young and old adults, but were present at lower levels in skeletal muscle and placenta. We suggest that they could represent intermediates of mtDNA repair, given their prevalence in the oxyradical-rich environment of heart muscle mitochondria.

DOI10.1093/embo-reports/kve233
Alternate JournalEMBO Rep.
Citation Key10.1093/embo-reports/kve233
PubMed ID11713192
PubMed Central IDPMC1084132
Grant ListMC_U105663140 / / Medical Research Council / United Kingdom