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Measuring mtDNA Mutation Rates in Saccharomyces cerevisiae Using the mtArg8 Assay

  • Micheline K. Strand
  • William C. Copeland
Part of the Methods in Molecular Biology™ book series (MIMB, volume 197)

Abstract

Mitochondrial mutation rates have historically been more refractory to genetic analysis than nuclear mutation rates. This is the result of the lack of auxotrophic genes in the mitochondria, the multiple (50-100) copies of mitochondrial genomes per cell (1), the random segregation of mitochondrial organelles during meiotic and mitotic cell division, and the apparent unequal replication of mitochondria (2).

Keywords

Mutation Rate Mitochondrial Genome Increase Copy Number Mitotic Cell Division Disruption Plasmid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Grimes, G. W., Mahler, H. R., and Perlman, R. S. (1974) Nuclear gene dosage effects on mitochondrial mass and DNA. J. Cell Biol. 61, 565–574.PubMedCrossRefGoogle Scholar
  2. 2.
    Davis, A. F. and Clayton, D. A. (1996) In situ localization of mitochondrial DNA replication in intact mammalian cells. J. Cell Biol. 135, 883–893.PubMedCrossRefGoogle Scholar
  3. 3.
    Ayala-Torres, S., Chen, Y., Svoboda, T., Rosenblatt, J., and Van Houten, B. (2000) Analysis of gene-specific DNA damage and repair using quantitative polymerase chain reaction. Methods 22, 135–147.PubMedCrossRefGoogle Scholar
  4. 4.
    Chen, T. J., Boles, R. G., and Wong, L. J. (1999) Detection of mitochondrial DNA mutations by temporal temperature gradient gel electrophoresis. Clin. Chem. 45, 1162–1167.PubMedGoogle Scholar
  5. 5.
    Khrapko, K., Coller, H. A., Andre, P. C., Li, X. C., Hanekamp, J. S., and Thilly, W. G. (1997) Mitochondrial mutational spectra in human cells and tissues. Proc. Natl.Acad. Sci. USA, 94, 13,798–13,803.PubMedCrossRefGoogle Scholar
  6. 6.
    Muniappan, B. P. and Thilly, W. G. (1999) Application of constant denaturant capillary electrophoresis (CDCE) to mutation detection in humans. Genet. Anal. 14, 221–227.PubMedGoogle Scholar
  7. 7.
    Salazar, J. J. and Van Houten, B. (1997) Preferential mitochondrial DNA injury caused by glucose oxidase as a steady generator of hydrogen peroxide in human fibroblasts. Mutat. Res. 385, 139–149.PubMedGoogle Scholar
  8. 8.
    Sor, F. and Fukuhara, H. (1984) Erythromycin and spiramycin resistance mutations of yeast mitochondria: nature of the rib2 locus in the large ribosomal RNA gene. Nucleic Acids Res. 12, 8313–8318.PubMedCrossRefGoogle Scholar
  9. 9.
    Strand, M. K., Stuart, G., Longley, M. J., Dominick, O. C., and Copeland, W. C. (2002) Identification of a kinase gene and characterization of its role in mitochondrial mutagenesis, submitted.Google Scholar
  10. 10.
    Senbongi, H., Ling, F., and Shibata, T. (1999) A mutation in a mitochondrial ABC transporter results in mitochondrial dysfunction through oxidative damage of mitochondrial DNA. Mol. Gen. Genet. 262, 426–436.PubMedCrossRefGoogle Scholar
  11. 11.
    Backer, J. and Foury, F. (1985) Repair properties in yeast mitochondrial DNA mutators. Curr. Genet. 10, 7–13.PubMedCrossRefGoogle Scholar
  12. 12.
    Steele, D. F., Butler, C. A., and Fox, T. D. (1996) Expression of a recoded nuclear gene inserted into yeast mitochondrial DNA is limited by mRNA-specific translational activation. Proc. Natl. Acad. Sci. USA 93, 5253–5257.PubMedCrossRefGoogle Scholar
  13. 13.
    Sia, E. A., Butler, C. A., Dominska, M., Greenwell, P., Fox, T. D., and Petes, T. D. (2000) Analysis of microsatellite mutations in the mitochondrial DNA of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 97, 250–255.PubMedCrossRefGoogle Scholar
  14. 14.
    Luria, S. E. and Delbruck, M. (1943) Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28, 491–511.PubMedGoogle Scholar
  15. 15.
    Lea, D. E. and Coulson, C. A. (1949) The distribution of the number of mutants in bacterial populations. J. Genet. 49, 264–285.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Micheline K. Strand
    • 1
  • William C. Copeland
    • 2
  1. 1.Laboratory of Molecular GeneticsNational Institute of Environmental Health Sciences
  2. 2.Laboratory of Molecular GeneticsNational Institute of Environmental Health Sciences, National Institutes of Health

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