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Scholars Day 2006, Wednesday, April 12

Role of Clu1p in Mitochondrial Genome Stability and Morphology in Budding Yeast

Mitochondrial genome maintenance is essential for the normal function of the cell. Mutations in mitochondrial DNA (mtDNA) lead to the loss of mitochondrial function and have been associated with a variety of human neuromuscular and age-related diseases. S. cerevisiae is a facultative anaerobe that can grow in the absence of respiration under specific growth conditions, although mitochondria are still required for viability. The lab used a yeast two-hybrid assay with the known mitochondrial protein, Ilv5p, to isolate genes involved in the organization, repair, and recombination of mtDNA. The lab has identified the Clu1p in this screen. Clu1p function was previously found to be required for proper mitochondrial morphology and distribution (1). Our data shows that a clu1∆ strain displays a 9.5 fold increased rate of respiration loss as evidenced by increased petite formation. This increase in petite formation may arise due to DNA polymerase slippage events at microsatellite tracts or an increase in mtDNA point mutations. Using clu1Ä::URA3 reporter strains, the lab has found a 1.6 fold increase in the rate of alterations in microsatellite tracts and a 2.1 fold increase in the rate at which mtDNA point mutations form. Using a recently developed direct-repeat-mediated deletion reporter strain, loss of Clu1p results in a 5.3 fold decrease in the rate of deletion formation relative to that of wild-type. Microscopy has supported previous reports indicating that a clu1∆ strain displays a “clustering” phenotype (1). This deletion strain exhibits a branched mitochondrial network that is localized to one side within the yeast cell. These data provide evidence that Clu1p plays a central role in mitochondrial genome stability and morphology. 1. Fields SD, Conrad MN, Clarke M. J Cell Sci. 1998 Jun;111 ( Pt 12):1717-27.

Presenter: Christine Hochmuth (Graduate Student)
Topic: Biological Sciences
Location: 216 Hartwell
Time: 2:30 pm (Session IV)

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Fri, Dec 5

Major Exploration Day
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