In our recent work we showed that EXOG is a multifunctional mitochondrial ribonuclease which facilitates the removal of RNA primer and supports the ligation of RNA-free ends. Our findings let us to propose a model of possible pathways that lead to the RNA primer removal and ligation during mitochondrial DNA replication. This includes the flap-independent pathway, where a coordinated action of EXOG and RNase H1 (RH1) is required, as well as the flap-dependent pathway, which requires a strand-displacement activity of Pol γ. Regardless the pathway, the nucleolytic activity of EXOG removes RNA remnants allowing for subsequent ligation by Lig III.
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In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing