Differential roles of Rad18 in repressing carcinogen- and oncogene-driven mutagenesis <i>in vivo</i>.

ABSTRACT: The DNA repair protein RAD18 activates "Y-family" trans-lesion synthesis (TLS) 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. Therefore, we tested the effect of Rad18 status on chemically induced and oncogene-driven tumorigenesis. In a chemically induced oral carcinogenesis model, acute (2-16 days) 4NQO treatment induces expression of Rad18 and TLS polymerase mRNAs in mouse oral epithelial cells prior to the emergence of oral squamous cell carcinomas (OSCCs). Chronic (8-week) 4NQO treatment leads to the onset of oral tumors that is accelerated in Rad18^-/-

SUBMITTER: Anand JR 

PROVIDER: S-EPMC12813500 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature