Abstract
A large number of gene products have been identified that either directly or indirectly alter the inheritance of mitochondrial DNA. In yeast, we have used a unique genetic screen based on the transfer of DNA from mitochondria to nucleus to identify nuclear-encoded gene products that are targeted to mitochondria and impact the stable inheritance of mitochondrial DNA. A specific allele of one of these genes, yme2-4, prevents even the low wild-type rate of mitochondrial DNA transfer to the nucleus and imparts significant temperature-sensitive and respiratory-growth defects. Intra- and extragenic suppressors of the yme2-4 growth phenotypes were isolated and analysis of these interacting genes reveals that both YME2 and its suppressors influence the structure and number of mitochondrial nucleoids. The yme2-4 allele decreases the average number of mtDNA nucleoids found in cells and the sensitivity of DNA in toluene-treated mitochondria to digestion by DNA exonuclease, effects reversed by intra- and extragenic suppressors. The extragenic suppressor, a missense allele of ILV5, encodes an enzyme of the branched-chain amino acid biosynthetic pathway that is also a component of mitochondrial nucleoids. A null allele of ILV5 suppresses transfer of mitochondrial DNA to the nucleus and displays synthetic interactions with yme2-4.
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Acknowledgments
We dedicate this work to the memory of Dr. Theodor Hanekamp. We thank Karen White, Brian Francis, Mary Brownson, and Christopher Smith for their many thoughtful suggestions. This work was supported by National Institutes of Health Grant GM047390.
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Communicated by Carla Koehler
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Park, S., Hanekamp, T., Thorsness, M.K. et al. Yme2p is a mediator of nucleoid structure and number in mitochondria of the yeast Saccharomyces cerevisiae . Curr Genet 50, 173–182 (2006). https://doi.org/10.1007/s00294-006-0087-9
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DOI: https://doi.org/10.1007/s00294-006-0087-9