biostudies-literatureHaines NMBiotechnology and Biological Sciences Research Council4037-42https://www.ebi.ac.uk/biostudies/studies/S-EPMC3964087biostudies-literatureUnknown111(11)Transcription-coupled nucleotide excision repair (TCR) accelerates the removal of noncoding lesions from the template strand of active genes, and hence contributes to genome-wide variations in mutation frequency. Current models for TCR suppose that a lesion must cause RNA polymerase (RNAP) to stall if it is to be a substrate for accelerated repair. We have examined the substrate requirements for TCR using a system in which transcription stalling and damage location can be uncoupled. We show that Mfd-dependent TCR in bacteria involves the formation of a damage search complex that can detect lesions downstream of a stalled RNAP, and that the strand specificity of the accelerated repair pathway is independent of the requirement for a lesion to stall RNAP. We also show that an ops (operon polaProceedings of the National Academy of Sciences of the United States of AmericaStalled transcription complexes promote DNA repair at a distance.PMC3964087BB/I001859/11095379BB/I003142/1Savery NJKim YIHaines NMSmith AJfalseStalled transcription complexes promote DNA repair at a distance.Transcription-coupled nucleotide excision repair (TCR) accelerates the removal of noncoding lesions from the template strand of active genes, and hence contributes to genome-wide variations in mutation frequency. Current models for TCR suppose that a lesion must cause RNA polymerase (RNAP) to stall if it is to be a substrate for accelerated repair. We have examined the substrate requirements for TCR using a system in which transcription stalling and damage location can be uncoupled. We show that Mfd-dependent TCR in bacteria involves the formation of a damage search complex that can detect lesions downstream of a stalled RNAP, and that the strand specificity of the accelerated repair pathway is independent of the requirement for a lesion to stall RNAP. We also show that an ops (operon pola2014-01-01T00:00:00Z2014 Mar2025-04-04T19:08:45.443Z2019-03-27T01:23:52ZS-EPMC39640872455407710.1073/pnas.1322350111