The yeast Holliday junction resolvase, CCE1, can restore wild-type mitochondrial DNA to human cells carrying rearranged mitochondrial DNA.

TitleThe yeast Holliday junction resolvase, CCE1, can restore wild-type mitochondrial DNA to human cells carrying rearranged mitochondrial DNA.
Publication TypeJournal Article
Year of Publication2007
AuthorsSembongi, H, Di Re, M, Bokori-Brown, M, Holt, IJ
JournalHum Mol Genet
Volume16
Issue19
Pagination2306-14
Date Published2007 Oct 01
ISSN0964-6906
KeywordsBlotting, Western, Cell Line, Tumor, DNA, Mitochondrial, Gene Dosage, Holliday Junction Resolvases, Humans, Microscopy, Confocal, Polymerase Chain Reaction, Recombination, Genetic, Saccharomyces cerevisiae Proteins, Transfection
Abstract

Rearrangements of mitochondrial DNA (mtDNA) are a well-recognized cause of human disease; deletions are more frequent, but duplications are more readily transmitted to offspring. In theory, partial duplications of mtDNA can be resolved to partially deleted and wild-type (WT) molecules, via homologous recombination. Therefore, the yeast CCE1 gene, encoding a Holliday junction resolvase, was introduced into cells carrying partially duplicated or partially triplicated mtDNA. Some cell lines carrying the CCE1 gene had substantial amounts of WT mtDNA suggesting that the enzyme can mediate intramolecular recombination in human mitochondria. However, high levels of expression of CCE1 frequently led to mtDNA loss, and so it is necessary to strictly regulate the expression of CCE1 in human cells to ensure the selection and maintenance of WT mtDNA.

DOI10.1093/hmg/ddm182
Alternate JournalHum. Mol. Genet.
Citation Key10.1093/hmg/ddm182
PubMed ID17666405
Grant ListMC_U105663140 / / Medical Research Council / United Kingdom