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Thesis (Ph. D.)--University of Rochester. Dept. of Biology, 2010.
The mitochondrial genome is a vital component of eukaryotic life. It is required for
the maintenance of respiration, which is essential for viability in all but a few eukary-
otic organisms. Unfortunately, like its counterpart in the nucleus, mitochondrial DNA
(mtDNA) is constantly being damaged by internal and external forces. It is believed
that mtDNA is especially susceptible to damage because of its close proximity to the
machinery responsible for oxidative phosphorylation. However, eukaryotes continue to
respire suggesting that, like the nucleus, the mitochondrion has mechanisms to main-
tain the stability of its genome in this presumably harsh environment. In this work, I
have examined the roles of several proteins that are important for this stability.
The mismatch repair protein MutS homolog Msh1p is essential for mitochondrial
function and stability of mtDNA. Msh1p is the only homolog of MutS that has been
found in the mitochondria. In the following dissertation, I will describe the work that
has been done to establish a role for Msh1p in the mitochondrial base excision repair
pathway, as well as examining the separation of function conferred by mutations to
di erent domains.
Pol4p is a polymerase in the X-family, and is the only polymerase of this family
found in Saccharomyces cerevisiae. We have shown that, as predicted by its similarity
to the human polymerase Pol , Pol4p is involved in the mitochondrial base excision
repair pathway. Mgm101p is crucial for stability of the mitochondrial genome, but its function
remains unkown. As part of the mitochondrial nucleoid, the possibilities for its role in
mtDNA maintenance are numerous. Our data suggest that Mgm101p forms a multimer
and may be modi ed by the small ubiquitin-like modi er protein SUMO.
