Common DNA damage sources of RNA polymerase pausing/blockage (shown in blue). Left, bulky (helix-distorting) DNA lesions such as those induced by solar radiation and endogenous/environmental genotoxins (see text for details). Middle, abortive cleavage complex intermediates of TOP1 (shown) or topoisomerase II (TOP2) arising endogenously during transcription or induced by chemotherapeutic topoisomerase poisons. Abortive topoisomerase cleavage complexes can lead to bona fide SSBs (TOP1/TOP2) and DSBs (TOP2) during transcription. Right, SSBs arising from attack of deoxyribose or nucleobases by reactive oxygen/nitrogen species, ionizing radiation, endogenous/environmental genotoxins, or during programmed base excision repair events (e.g., epigenetic reprogramming). Note that only SSBs with aberrant 5' and/or 3' termini (red circles), such as 3'-phosphate termini, appear to strongly pause/block RNA polymerase progression.
