title: A mitochondrial mutator plasmid that causes senescence under dietary restricted conditions.
abstract: BACKGROUND
  Calorie or dietary restriction extends life span in a wide range of organisms including the filamentous fungus Podospora anserina. Under dietary restricted conditions, P. anserina isolates are several-fold longer lived. This is however not the case in isolates that carry one of the pAL2-1 homologous mitochondrial plasmids.
  
  
  RESULTS
  We show that the pAL2-1 homologues act as 'insertional mutators' of the mitochondrial genome, which may explain their negative effect on life span extension. Sequencing revealed at least fourteen unique plasmid integration sites, of which twelve were located within the mitochondrial genome and two within copies of the plasmid itself. The plasmids were able to integrate in their entirety, via a non-homologous mode of recombination. Some of the integrated plasmid copies were truncated, which probably resulted from secondary, post-integrative, recombination processes. Integration sites were predominantly located within and surrounding the region containing the mitochondrial rDNA loci.
  
  
  CONCLUSIONS
  We propose a model for the mechanism of integration, based on innate modes of mtDNA recombination, and discuss its possible link with the plasmid's negative effect on dietary restriction mediated life span extension.
authors.affiliation: Centre de Génétique Moléculaire, Centre Nationale de la Recherche Scientifique, Gif-sur-Yvette, France. Maas@cgm.cnrs-gif.fr
authors.forename: Marc F P M
authors.initials: MF
authors.lastname: Maas
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Hoekstra
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: Debets
mesh_terms: D031204:Caloric Restriction; D003470:Culture Media; D004271:DNA, Fungal / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D016254:Mutagenesis, Insertional; D010957:Plasmids; D048468:Podospora / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011995:Recombination, Genetic
chemical_list: D003470:Culture Media; D004271:DNA, Fungal; D004272:DNA, Mitochondrial