Transcription coupled repair efficiency determines the cell cycle progression and apoptosis after UV exposure in hamster cells.

Nucleotide excision repair (NER) is a major pathway for the removal of bulky adducts and helix distorting lesions from the genomic DNA. NER is highly heterogeneous across the genome and operates principally at different levels of hierarchy. Transcription coupled repair (TCR), a special sub-pathway of NER and base excision repair (BER), is critical for cellular resistance after UV irradiation in mammalian cells. In this study, we have investigated the effects of UV-C irradiation on cell cycle progression and apoptosis in G1 synchronised isogenic hamster cell lines that are deficient in TCR and NER pathways. Our results revealed the existence of two apoptotic modes at low UV (2-4J/m2) doses in TCR deficient (UV61) and NER deficient (UV5) cells: one occurring in the first G1 and the other in the second G1-phase following the first division. At high UV doses (8-32J/m2), UV61 and UV5 cells underwent apoptosis without entry into S-phase after a permanent arrest in the initial G1. In contrast to repair deficient cells, parental TCR proficient AA8 cells did not show a significant G1 arrest and apoptosis at doses below 8J/m2. UV61 (proficient in repair of 6-4 photoproducts (PPs)) and UV5 (deficient in 6-4 PP repair) cells showed similar patterns of cell cycle progression and apoptosis. Taken together, these results suggest that the persistence of 6-4 PP and the replication inhibition may not be critical for apoptotic response in hamster cells. Instead, the extent of transcription blockage resulting from the TCR deficiency constitutes the major determining factor for G1 arrest and apoptosis.