Analysis of the functional domains of the mismatch repair homologue Msh1p and its role in mitochondrial genome maintenance.
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.
Mookerjee
Shona A
SA
Department of Biology, University of Rochester, RC Box 270211, Rochester, NY 14627-0211, USA.
Lyon
Hiram D
HD
Sia
Elaine A
EA
D000595:Amino Acid Sequence; D020137:Base Pair Mismatch; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D016681:Genome, Fungal; D008856:Microscopy, Fluorescence; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D010957:Plasmids; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C078660:MSH1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins