Impact of RAD18 Status and 4NQO on Genome Integrity

The DNA repair protein RAD18 activates Trans-Lesion Synthesis DNA polymerases that are DNA damage-tolerant and potentially error-prone. RAD18 is also frequently overexpressed and pathologically activated in cancer cells. However, the extent to which RAD18 shapes cancer genomes and impacts tumorigenesis is unclear. The impact of RAD18 status and Trans-Lesion Synthesis in a chemically-induced oral carcinogenesis model on genomic integrity is tested in this project. Wild type, RAD18 -/+, and RAD18-/- mice received 50 ug/ml 4-Nitroquinoline N-oxide (4NQO) dissolved in 20 ug/ml 1,2 propanediol (propylene glycol) diluted with sterile water and resultant oral tumors and matched normal tailed were harvested and sequenced.