DNA damage results in the up-regulation of several genes involved in different 
cellular physiological processes, such as the nucleotide excision repair (NER) 
mechanism that copes with a broad range of DNA alterations, including the 
carcinogenic ultraviolet (UV) light-induced pyrimidine dimers (PDs). There are 
two NER sub-pathways: transcription coupled repair (TCR) that is specific for 
the transcribed strands (TS) of active genes and global genomic repair (GGR) 
that repairs non-transcribed DNA sequences (NTD) and the non-transcribed strands 
(NTS) of expressed genes. To elucidate the role of UV-dependent de novo protein 
synthesis in nucleotide excision repair in the budding yeast, we investigated 
the effect of the protein synthesis inhibitor, cycloheximide, on the removal of 
PDs. Log phase as well as G(1)-synchronized cells were treated with the drug 
shortly before UV irradiation and immediately thereafter, and the repair of 
damaged DNA was assessed with the high resolution primer extension technique. 
The results show that in both cellular conditions, the inhibition of 
UV-dependent de novo protein synthesis by cycloheximide impairs the excision 
repair of the transcriptionally active GAL10 and URA3 genes, with a greater 
effect on the non-transcribed strands. This indicates that UV-mediated de novo 
protein synthesis is required for efficient nucleotide excision repair, but not 
for the preferential repair of the TSs. On the other hand, cycloheximide did not 
affect the repair of either strand of the repressed GAL10 gene or the 
non-transcribed promoter region of the URA3 gene, showing that UV-induced de 
novo protein synthesis is not required for PD removal from transcriptionally 
inactive DNA sequences. Together, these data show that despite the fact that NTD 
and NTSs are normally repaired by the GGR sub-pathway, their requirement for 
UV-dependent de novo protein synthesis is different, which may suggest a 
difference in the processing of UV lesions in these non-transcribed sequences of 
the genome.