Linking transcription with DNA repair, damage tolerance, and genome duplication

The transcription of genes by RNA polymerases (RNAPs) is far from a smooth ride. Not only is template sequence-dependent pausing of RNAPs a frequent occurrence (1), lesions within the transcribed strand present major barriers to continued movement of RNAPs, with potentially disastrous consequences for gene expression (2). To make matters worse, such stalled transcription complexes mask the DNA damage from recognition and removal by repair systems (3) (Fig. 1A). Transcription-coupled repair (TCR) provides a solution to this problem by recruiting repair enzymes to RNAPs blocked by lesions, the outcome being preferential repair of DNA damage within the transcribed strand of expressed genes (4, 5). The transcription repair coupling factor in Escherichia coli, Mfd, is the best-characterized example of such coupling and has provided a paradigm for TCR in other organisms (6) (Fig. 1B). A report in PNAS indicates that a second, very different, type of TCR also exists. Cohen et al. (7) demonstrate that a transcription elongation factor, NusA, promotes an Mfd-independent pathway of TCR in E. coli, providing an explanation for the mild damage sensitivity of cells lacking Mfd and suggesting that a second mechanism of TCR could be operative in other organisms. Their work also points to NusA as being a central player in coordination of transcription, DNA repair, damage tolerance, and genome stability.