Transcription coupled repair of 8-oxoguanine in murine cells: The Ogg1 protein is required for repair in nontranscribed sequences but not in transcribed sequences

To assess the role of the Ogg1 DNA glycosylase in the transcription-coupled repair (TCR) of the mutagenic lesion, 7.8-dihydro-8-oxoguanine (8-OxoC), we have investigated the removal of this lesion in wild-type and ogg1(-/-) null mouse embryo fibroblast (MEF) cell lines. We used nonreplicating plasmids containing a single 8-OxoG-C base pair in a different assay that allowed us to study the removal of 8-OxoG located in a transcribed sequence (TS) or in a nontranscribed sequence (NTS). The results show that the removal of 8-OxoG in a wild-type MEF cell line is faster in the TS than in the NTS. indicating TCR of 8-OxoG in murine cells. In the homozygous ogg1(-/-) MEF cell line. 8-OxoC was not removed from the NTs whereas there was still efficient 8-OxoG repair in the TS, Expression of the mouse Ogg1 protein in the homozygous ogg1(-/-) cell line restored the ability to remove 8-OxoC in the NTS. Therefore, we have demonstrated that Ogg1 is essential for the repair of 8-OxoC in the NTs but is not required in the TS. These results indicate the existence of an Ogg1-independent pathway for the TCR of 8-OxoC in vivo.