Double-stranded DNA-dependent ATPase Irc3p is directly involved in mitochondrial genome maintenance.
Nucleic acid-dependent ATPases are involved in nearly all aspects of DNA and RNA metabolism. Previous studies have described a number of mitochondrial helicases. However, double-stranded DNA-dependent ATPases, including translocases or enzymes remodeling DNA-protein complexes, have not been identified in mitochondria of the yeast Saccharomyces cerevisae. Here, we demonstrate that Irc3p is a mitochondrial double-stranded DNA-dependent ATPase of the Superfamily II. In contrast to the other mitochondrial Superfamily II enzymes Mss116p, Suv3p and Mrh4p, which are RNA helicases, Irc3p has a direct role in mitochondrial DNA (mtDNA) maintenance. Specific Irc3p-dependent mtDNA metabolic intermediates can be detected, including high levels of double-stranded DNA breaks that accumulate in irc3Δ mutants. irc3Δ-related topology changes in rho- mtDNA can be reversed by the deletion of mitochondrial RNA polymerase RPO41, suggesting that Irc3p counterbalances adverse effects of transcription on mitochondrial genome stability.
Institute of Molecular and Cell Biology, University of Tartu, Riia 23b, Tartu 51010, Estonia.
Tiina
T
Sedman
Institute of Molecular and Cell Biology, University of Tartu, Riia 23b, Tartu 51010, Estonia.
Ilja
I
Gaidutšik
Institute of Molecular and Cell Biology, University of Tartu, Riia 23b, Tartu 51010, Estonia.
Karin
K
Villemson
Institute of Molecular and Cell Biology, University of Tartu, Riia 23b, Tartu 51010, Estonia.
YingJian
Y
Hou
Institute of Molecular and Cell Biology, University of Tartu, Riia 23b, Tartu 51010, Estonia juhan.sedman@ut.ee.
Juhan
J
Sedman
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D004843:Epistasis, Genetic; D054629:Genome, Mitochondrial; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D012321:DNA-Directed RNA Polymerases; C487996:RPO41 protein, S cerevisiae; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C000594746:Irc3 protein, S cerevisiae