Brief Communication abstract


Nature Genetics 40, 392 - 394 (2008)
Published online: 2 March 2008 | doi:10.1038/ng.95

DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice

Marc Vermulst1, Jonathan Wanagat2, Gregory C Kujoth3, Jason H Bielas1, Peter S Rabinovitch1, Tomas A Prolla3 & Lawrence A Loeb1

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Mitochondrial DNA (mtDNA) mutations are thought to have a causal role in many age-related pathologies. Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-directed DNA repair mechanism in mitochondria that is directly linked to the formation of mtDNA deletions. In addition, our results demonstrate that the rate at which mtDNA mutations reach phenotypic expression differs markedly among tissues, which may be an important factor in determining the tolerance of a tissue to random mitochondrial mutagenesis.

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  1. Department of Pathology, University of Washington, Seattle, 91895 Washington, USA.
  2. Department of Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington 91895, USA.
  3. Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA.

Correspondence to: Lawrence A Loeb1 e-mail: laloeb@u.washington.edu



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