Figure 8.

A model of RITOLS replication of mtDNA. RNA incorporation throughout the lagging strand (RITOLS) may be attributed either to synthesis by a primase (see Discussion) or (panel 1) to the incorporation of preformed RNA (the bootlace model). As the fork advances (from diagram a to b to c), preformed RNA is threaded through the replication complex in the 3′–5′ direction, hybridized with the displaced parental strand. Panel 2: replication initiates in an effectively unidirectional manner at a discrete origin O_R (located either at O_H or in the distal portion of the NCR). The lagging strand is laid down initially as RNA (red). In some molecules, the entire lagging strand is incorporated as RNA before conversion to DNA commences (A). Other molecules initiate maturation approximately two-thirds of the way around the genome (B), or at dispersed sites (C). In chicken liver mtDNA, maturation is a mixture of A and C, whereas maturation of mouse liver mtDNA occurs predominantly in the vicinity of O_L (scheme B). Such a model can generate the arcs of RIs detected in the experiments presented in this paper.