The Keith Peters Building
Molecular basis of mitochondrial DNA replication in mammalian cells.
Human mitochondria contain a small double-stranded DNA genome (mtDNA). The genome is dense in information and contains genes for 2 rRNAs, 22 tRNAs, and 13 mRNAs that code for components of the respiratory chain. Loss of mtDNA or mutations can cause a number of different mitochondrial diseases. The mitochondrial replisome contains four essential factors: DNA polymerase γ, the DNA helicase TWINKLE, the mitochondrial single stranded DNA binding protein, mtSSB, and the mitochondrial RNA polymerase, POLRMT, which synthesizes primers required for initiation of mtDNA synthesis. Recently, two additional proteins, MGME1 and RNase H1 were also shown to be involved in mtDNA replication. I will discuss how these factors cooperate to replicate the mitochondrial genome. I will also discuss how disease-causing mutations in the different proteins can affect the function of this molecular machinery.