Behaviour of a population of partially duplicated mitochondrial DNA molecules in cell culture: segregation, maintenance and recombination dependent upon nuclear background |
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Authors: | Holt, IJ Dunbar, DR Jacobs, HT |
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Affiliation: | Department of Molecular Pathology, University of Dundee, Ninewells Medical School, UK. i.j.holt@dundee.ac.uk |
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Abstract: | We have studied the dynamics of mitochondrial DNA maintenance andsegregation in human cells using serial cybrid transfer of partiallyduplicated mitochondrial DNA, from a mitochondrial myopathy patient, to twodistinct recipient cell types. The results indicate two radically differentoutcomes dependent upon nuclear background. In one case (lung carcinoma)there is systematic loss of the partial duplication by an impliedrecombinational mechanism. In another nuclear background (osteosarcoma) theduplicated molecules can survive, having only a marginal effect onmitochondrial respiratory function. Moreover, in the osteosarcoma nuclearbackground further disturbances of mtDNA maintenance frequently follow fromcybrid transfer. These are progressive, catastrophic loss of mtDNA andfurther rearrangement to generate partially triplicated molecules. Theresults imply differential expression of nuclear genes regulating mtDNAcopy number, replication and recombination in different human cell types. |
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