Fig. 5: Autoregulation of Twinkle activities by the ZBD and C-terminal tail.
From: Autoregulation of the real-time kinetics of the human mitochondrial replicative helicase
Twinkle scans DNA to locate the fork junction through diffusion. In the absence of mtSSB, ZBD-DNA interactions restrict functional loading at the fork and promote pauses (and rewinding events) during DNA unwinding. During this reaction, the C-tail downregulates ATP turnover, leading to additional pauses and reduced DNA unwinding rate. In the presence of mtSSB, interactions between the mtSSB and the C-terminal tail facilitate functional loading of the helicase onto the fork. mtSSB binding to the translocation strand outcompetes the inhibitory ZBD-DNA interactions, enhancing functional loading, decreasing pause occupancy during DNA unwinding, and reducing the probability of rewinding events.
