Heterogeneity of DNA repair has been observed at different levels of genomic 
organization, including chromatin domains, expressed genes and DNA strands. If 
heterogeneity also existed intragenically, it could reveal fine details of the 
excision repair mechanism in vivo. Here we measure the frequency of UV-induced 
cyclobutane pyrimidine dimers at individual nucleotides within defined portions 
of two Escherichia coli genes, lacl and lacZ, at various times after 
irradiation. Two domains of differential repair rates were apparent, with repair 
being slow at nucleotides adjacent to the transcription start sites. In lacZ, 
the domain of faster repair began 32 bases downstream of the transcription start 
site and required the mfd gene. Since mfd codes for a transcription-repair 
coupling factor, this transcription-coupled repair system evidently becomes 
operative downstream of the initiation complex region in vivo. Unexpectedly, 
however, (1) an mfd mutation reduced repair in the downstream domain even when 
transcription was at a very low level and (2) induction of lacZ transcription 
with isopropyl-beta-D-thiogalactoside overcame this reduction. Evidently, the 
Mfd transcription-repair coupling factor is required for basal levels of 
strand-specific repair in this gene, but induced levels of repair are related to 
transcription through another mechanism.