Figure 6.

Model of the ExoG-mediated RNA primer removal process during mtDNA replication. RNase H1 degrades most of the long RNA primers but leaves two RNA nucleotides (2-RNA-nt) at the 5′ end of the newly synthesized DNA during H-strand replication. The two RNA nucleotides could be displaced by Polγ and then resolved by FEN1, DNA2 and/or MGME1 in a flap-dependent manner. Alternatively, ExoG removes this 5′-end RNA dinucleotide from the hybrid duplex in a flap-independent manner. RNA primers are represented by red lines. Template and newly synthesized DNA are shown as black and blue lines, respectively. Black scissors indicate enzyme cleavage sites.