Doctoral defence: Sirelin Sillamaa "The role of helicases Hmi1 and lrc3 in yeast mitochondrial DNA maintenance"

On 11 June at 10:15 Sirelin Sillamaa will defend her doctoral thesis “The role of helicases Hmi1 and lrc3 in yeast mitochondrial DNA maintenance“ for obtaining the degree of Doctor of Philosophy (in Biochemistry). 

Supervisors:
Professor Juhan Sedman, University of Tartu
Associate professor Priit Jõers, University of Tartu

Opponent:
Professor Pawel Golik, University of Warsaw (Poland)

Summary
Mitochondrion is a multifunctional organelle best known for its role in oxidative phosphorylation through maintaining the respiratory chain. Although most of the proteins needed for the assembly of the respiratory chain are encoded by the nuclear genome, a handful of proteins are also encoded by small mitochondrial genome. Therefore, it is important to maintain the functional mitochondrial DNA, as its loss can lead to cell death. Furthermore, even small mitochondrial genome rearrangements have been associated with different human diseases. 

Some species, like baker’s yeast Saccharomyces cerevisiae, can survive without any or with nonfunctional mitochondrial DNA, making it a good model system for observing the effects on mtDNA integrity. One group of proteins required for mtDNA maintenance are helicases, which use ATP energy for unwinding different nucleic acid structures. 

The present thesis focuses on the function of mitochondrial DNA helicases Hmi1 and Irc3. The results show, that Irc3-like helicases are important for modifying the branched DNA molecules and preventing the accumulation of damaged and broken DNA molecules, which in time would lead to the loss of mitochondrial DNA. In addition, Irc3-like helicases also participate in RNA metabolism, a function that might also affect mtDNA maintenance. Hmi1 is a helicase essential for the maintenance of the functional mitochondrial genome of S. cerevisiae. Unlike most helicases, ATP hydrolysis is partially dispensable for the Hmi1 function. The results of this thesis indicate, that Hmi1 has ATP hydrolysis dependent and independent function in the cell.

Collectively, the results of this thesis show how diverse are the mitochondrial helicases and give an insight into the complex system of maintaining the mitochondrial DNA.