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Analysis of the functional domains of the mismatch repair homologue Msh1p and its role in mitochondrial genome maintenance

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Abstract

Mitochondrial DNA (mtDNA) repair occurs in all eukaryotic organisms and is essential for the maintenance of mitochondrial function. Evidence from both humans and yeast suggests that mismatch repair is one of the pathways that functions in overall mtDNA stability. In the mitochondria of the yeast Saccharomyces cerevisiae, the presence of a homologue to the bacterial MutS mismatch repair protein, MSH1, has long been known to be essential for mitochondrial function. The mechanisms for which it is essential are unclear, however. Here, we analyze the effects of two point mutations, msh1-F105A and msh1-G776D, both predicted to be defective in mismatch repair; and we show that they are both able to maintain partial mitochondrial function. Moreover, there are significant differences in the severity of mitochondrial disruption between the two mutants that suggest multiple roles for Msh1p in addition to mismatch repair. Our overall findings suggest that these additional predicted functions of Msh1p, including recombination surveillance and heteroduplex rejection, may be primarily responsible for its essential role in mtDNA stability.

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Acknowledgements

This work was supported by the National Institutes of Health grant GM63626-01. E.A.S. is the recipient of a Burroughs–Wellcome Fund Career Award. Purchase of the Leica TCS SP spectral confocal microscope was supported by shared instrumentation awards from the National Science Foundation (9512886) and the National Institute of Health (S10RR11358) and by matching funds from the University of Rochester. We would like to thank Dr. Rita Miller for use of the Zeiss Axioplan 2 microscope. We would also like to thank Leah Jablonski for construction of the msh1-G776D mutation.

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  1. Department of Biology, University of Rochester, RC Box 270211, Rochester, NY 14627-0211, USA

    Shona A. Mookerjee, Hiram D. Lyon & Elaine A. Sia

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  1. Shona A. Mookerjee
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  2. Hiram D. Lyon
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  3. Elaine A. Sia
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Correspondence to Elaine A. Sia.

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Communicated by M. Brunner

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Mookerjee, S.A., Lyon, H.D. & Sia, E.A. Analysis of the functional domains of the mismatch repair homologue Msh1p and its role in mitochondrial genome maintenance. Curr Genet 47, 84–99 (2005). https://doi.org/10.1007/s00294-004-0537-1

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