Intra- and inter-molecular recombination of mitochondrial DNA after in vivo induction of multiple double-strand breaks.

ABSTRACT: To investigate mtDNA recombination induced by multiple double strand breaks (DSBs) we used a mitochondria-targeted form of the ScaI restriction endonuclease to introduce DSBs in heteroplasmic mice and cells in which we were able to utilize haplotype differences to trace the origin of recombined molecules. ScaI cleaves multiple sites in each haplotype of the heteroplasmic mice (five in NZB and three in BALB mtDNA) and prolonged expression causes severe mtDNA depletion. After a short pulse of restriction enzyme expression followed by a long period of recovery, mitochondrial genomes with large deletions were detected by PCR. Curiously, we found that some ScaI sites were more commonly involved in recombined molecules than others. In intra-molecular recombination events, deletion breakpoints we

SUBMITTER: Bacman SR 

PROVIDER: S-EPMC2715231 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature