Transcription coupled repair (TCR), a special sub-pathway of nucleotide excision 
repair (NER), removes transcription blocking lesions rapidly from the 
transcribing strand of active genes. In this study, we have evaluated the 
importance of the TCR pathway in the induction of chromosomal aberrations and 
apoptosis in isogenic Chinese hamster cell lines, which differ in TCR 
efficiency. AA8 is the parental cell line, which is proficient in the genome 
overall repair of UV-C radiation induced 6-4 photoproducts (6-4 PP) and the 
repair of cyclobutane pyrimidine dimer (CPD) from the transcribing strand of 
active genes. UV61 cells (hamster homologue of human Cockayne's syndrome (CS) 
group B cells) originally isolated from AA8, exhibit proficient repair of 6-4 PP 
but are deficient in CPD removal by the TCR pathway. Upon UV-C irradiation of 
cells in G1-phase, UV61 showed a dramatic increase in apoptotic response as 
compared to AA8 cells. Abolition of TCR by treatment with alpha-amanitin (an 
inhibitor of RNA polymerase II) in AA8 cells also resulted in an elevated 
apoptotic response like that observed in UV61 cells treated with UV alone. This 
suggests that the lack of TCR is largely responsible for increased apoptotic 
response in UV61 cells. Furthermore, the chromosomal aberrations and sister 
chromatid exchange (SCE) induced by UV were also found to be higher in UV61 
cells than in TCR proficient AA8 cells. This study shows that the increased 
chromosomal aberrations and apoptotic death in UV61 cells is due to their 
inability to remove CPD from the transcribing strand of active genes and 
suggests a protective role for TCR in the prevention of both chromosomal 
aberrations and apoptosis induced by DNA damage. Furthermore, flow cytometry 
analysis and time-course appearance of apoptotic cells suggest that the 
conversion of UV-DNA damage into chromosomal aberrations precedes and determines 
the apoptotic process.