A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in Caenorhabditis elegans

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Lewis , S C , Joers , P , Willcox , S , Griffith , J D , Jacobs , H T & Hyman , B C 2015 , ' A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in Caenorhabditis elegans ' PLoS Genetics , vol. 11 , no. 2 , 1004985 . DOI: 10.1371/journal.pgen.1004985

Title: A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in Caenorhabditis elegans
Author: Lewis, Samantha C.; Joers, Priit; Willcox, Smaranda; Griffith, Jack D.; Jacobs, Howard T.; Hyman, Bradley C.
Other contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Research Programme for Molecular Neurology

Date: 2015-02
Language: eng
Number of pages: 16
Belongs to series: PLoS Genetics
ISSN: 1553-7390
DOI: https://doi.org/10.1371/journal.pgen.1004985
URI: http://hdl.handle.net/10138/162485
Abstract: Mitochondrial DNA (mtDNA) encodes respiratory complex subunits essential to almost all eukaryotes; hence respiratory competence requires faithful duplication of this molecule. However, the mechanism(s) of its synthesis remain hotly debated. Here we have developed Caenorhabditis elegans as a convenient animal model for the study of metazoan mtDNA synthesis. We demonstrate that C. elegans mtDNA replicates exclusively by a phage-like mechanism, in which multimeric molecules are synthesized from a circular template. In contrast to previous mammalian studies, we found that mtDNA synthesis in the C. elegans gonad produces branched-circular lariat structures with multimeric DNA tails; we were able to detect multimers up to four mtDNA genome unit lengths. Further, we did not detect elongation from a displacement-loop or analogue of 7S DNA, suggesting a clear difference from human mtDNA in regard to the site(s) of replication initiation. We also identified cruciform mtDNA species that are sensitive to cleavage by the resolvase RusA; we suggest these four-way junctions may have a role in concatemer-to-monomer resolution. Overall these results indicate that mtDNA synthesis in C. elegans does not conform to any previously documented metazoan mtDNA replication mechanism, but instead are strongly suggestive of rolling circle replication, as employed by bacteriophages. As several components of the metazoan mitochondrial DNA replisome are likely phage-derived, these findings raise the possibility that the rolling circle mtDNA replication mechanism may be ancestral among metazoans.
Subject: C-ELEGANS
HOMOLOGOUS RECOMBINATION
YEAST MITOCHONDRIA
LAGGING-STRAND
IN-VIVO
GENOME
MTDNA
MAINTENANCE
JUNCTIONS
HEMICATENANES
1184 Genetics, developmental biology, physiology
3112 Neurosciences
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