The in vivo role of Rev1 in mutagenesis and carcinogenesis

Abstract

Translesion synthesis (TLS) is an error-prone pathway required to overcome replication blockage by DNA damage. Aberrant activation of TLS has been suggested to play a role in tumorigenesis by promoting genetic mutations. However, the precise molecular mechanisms underlying TLS-mediated tumorigenesis in vivo remain unclear. Rev1 is a member of the Y family polymerases and plays a key role in the TLS pathway. Here we introduce the existing to date Rev1-mutated mouse models, including the Rev1 transgenic (Tg) mouse model generated in our laboratory. We give an overview of the current knowledge on how different disruptions in Rev1 functions impact mutagenesis and the suggested molecular mechanisms underlying these effects. We summarize the available data from ours and others' in vivo studies on the role of Rev1 in the initiation and promotion of cancer, emphasizing how Rev1-mutated mouse models can be used as complementary tools for future research.