An integrated mechanistic model for transcription-coupled nucleotide excision repair

Abstract

Preferential repair of the transcribed strand of active genes is usually attributed to a coupling protein that dislodges RNA polymerase stalled at a damage site and recruits repair enzymes. Experimental observations of the effect of transcription on preferential repair in Escherichia coli are contradictory and inexplicable by this model. In this study, it is argued that the multiple conformations displayed by a stalled RNA polymerase result in two sub-pathways for repair: Mfd coupled and direct. Together with the fact that RNA polymerase recruits the repair enzymes in a promoter dependent manner, an integrated mechanistic model is proposed that is capable of explaining the effect of transcription on preferential repair reported in literature. The quantitative behavior of the model is illustrated by describing the various reactions using a biochemical network. The implications of the model on the mechanism for transcription-coupled repair in higher organisms are briefly discussed.