Transcription-coupled repair: a multifunctional signaling pathway.

Abstract

It is well established that certain types of DNA damage, for example, UV-induced pyrimidine dimers, blockthe progression of RNA polymerase. Evidence suggesting a relationship between DNA repair and transcriptionwas presented by Mayne and Lehmann (1982), who observed that the recovery of RNA synthesis was morerapid than the overall time course of DNA repair in UVirradiated human cells. In addition, it was found that although Cockayne syndrome (CS) cells were able to carryout normal levels of repair synthesis, they were unable torecover their RNA synthesis after UV irradiation. Thus, itwas suggested that the defect in CS cells resides in the repair of damage in transcribed genes. There is now a largebody of evidence showing that damage produced by UVand certain chemical carcinogens is repaired more rapidlyin transcriptionally active DNA compared to the genomeas a whole. This rapid repair was originally shown to bedue to a faster repair of damage in the transcribed strandthan in the nontranscribed strand in both hamster and human genes (Mellon et al. 1987; Leadon and Lawrence1991). Although strand-specific repair of UV damagewas originally demonstrated in mammalian cells, it hasnow also been confirmed in Escherichia coli (Mellon andHanawalt 1989) and Saccharomyces cerevisiae (Smerdon et al. 1990; Leadon and Lawrence 1992; Sweder andHanawalt 1992) and hence appears to be a highly conserved pathway for excision repair...