Transcription and DNA adducts: what happens when the message gets cut off?

DNA damage located within a gene's transcription unit can cause RNA polymerase to stall at the modified site, resulting in a truncated transcript, or progress past, producing full-length RNA. However, it is not immediately apparent why some lesions pose strong barriers to elongation while others do not. Studies using site-specifically damaged DNA templates have demonstrated that a wide range of lesions can impede the progress of elongating transcription complexes. The collected results of this work provide evidence for the idea that subtle structural elements can influence how an RNA polymerase behaves when it encounters a DNA adduct during elongation. These elements include: (1) the ability of the RNA polymerase active site to accommodate the damaged base; (2) the size and shape of the adduct, which includes the specific modified base; (3) the stereochemistry of the adduct; (4) the base incorporated into the growing transcript; and (5) the local DNA sequence.