Impact of MAGE-A4 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. MAGE-A4 induces RAD18 expression and sustains Trans-Lesion Synthesis in cancer cells. However, the extent to which RAD18 and MAGE-A4 shapes cancer genomes and impacts tumorigenesis is unclear. The impact of MAGE-A4 status and Trans-Lesion Synthesis in a chemically-induced oral carcinogenesis model on genomic integrity is tested in this project. Wild type, and Cre-inducible MAGE-A4 expressing 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.