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


Defects in the mitochondrial DNA (mtDNA) that encodes protein subunits of the respiratory complexes may cause severe metabolic disease in humans. Such defects are often caused by errors during mtDNA synthesis, motivating ongoing studies of this process. The nematode Caenorhabditis elegans has been proposed as a model for the study of mtDNA replication defects. Here we analyze the mechanism of mtDNA synthesis in the C. elegans gonad and demonstrate that it is unique among animals. Nascent worm mtDNA forms branched-circular lariat structures with concatemeric tails that we suggest would ultimately resolve into monomeric circles, the predominant molecular form identified by both transmission electron microscopy and two-dimensional gel electrophoresis. Our discovery that mtDNA replication in C. elegans does not faithfully model that in mammals is significant, because it demonstrates the breadth and evolutionary plasticity of the mechanisms that maintain this critical DNA among animals. Interestingly, the mtDNA replication mechanism within C. elegans is highly similar to that of bacteriophages, from which components of the mitochondrial DNA replisome are thought to be derived. Thus C. elegans may serve as a model for mtDNA synthesis as it occurred within ancient eukaryotes.


Vyšlo v časopise: A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004985
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004985

Souhrn

Defects in the mitochondrial DNA (mtDNA) that encodes protein subunits of the respiratory complexes may cause severe metabolic disease in humans. Such defects are often caused by errors during mtDNA synthesis, motivating ongoing studies of this process. The nematode Caenorhabditis elegans has been proposed as a model for the study of mtDNA replication defects. Here we analyze the mechanism of mtDNA synthesis in the C. elegans gonad and demonstrate that it is unique among animals. Nascent worm mtDNA forms branched-circular lariat structures with concatemeric tails that we suggest would ultimately resolve into monomeric circles, the predominant molecular form identified by both transmission electron microscopy and two-dimensional gel electrophoresis. Our discovery that mtDNA replication in C. elegans does not faithfully model that in mammals is significant, because it demonstrates the breadth and evolutionary plasticity of the mechanisms that maintain this critical DNA among animals. Interestingly, the mtDNA replication mechanism within C. elegans is highly similar to that of bacteriophages, from which components of the mitochondrial DNA replisome are thought to be derived. Thus C. elegans may serve as a model for mtDNA synthesis as it occurred within ancient eukaryotes.


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