Figure 2.Cis- and trans-acting factors affecting translocation. (A) Structure of RNA-DNA hybrid and dsDNA in TEC by T. thermophilus (Tth) RNAP. The structural targets for translocation regulators are indicated by arrows. (B) A schematic structure of TEC: RNAP (blue oval), upstream and downstream dsDNA (gray cylinders), RNA-DNA hybrid (brown cylinder), transcription bubble (black line) and the bridge helix (green) are shown; the active center in RNAP is represented by a circle with i and i+1 subsites. The inset displays the pre-translocated configuration of the active center with DNA lesion in i site (yellow triangle) and the 3′ RNA residue in a frayed configuration in i+1 site. The left side shows cis-acting translocation inhibitors: bending, or other structural alteration of the hybrid, the front-end DNA duplex and hairpin in the nascent RNA interacting with RNAP (shown by curved arrow). The right side displays the trans-acting inhibitors: a drug molecule bound to bridge helix reducing its mobility/bending (red dot), protein factors bound to dsDNA, nascent RNA or RNAP, and the second RNAP molecule in a head-to-tail configuration (all in magenta).