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Molecular basis of mitochondrial DNA replication in mammalian cells

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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.

This talk is part of the MRC Mitochondrial Biology Unit Seminars series.

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