Translesion synthesis by RNA polymerases: occurrence and biological implications for transcriptional mutagenesis

Abstract

The genes of all organisms are continuously damaged by extrinsic and intrinsic physical and chemical agents. If the resulting DNA damage is left unrepaired, a number of deleterious biological consequences may result including the production of mutant proteins which can change the cellular phenotype. The majority of DNA damage-induced mutagenesis studies are based on models of DNA polymerase errors occurring in the vicinity of the lesion. In contrast, few studies have addressed the possibility that mutagenesis at the level of transcription (i.e. when RNA polymerase bypasses a lesion and a misincorporation event occurs) may also be an important source of mutant proteins, particularly in nondividing cell populations. This article reviews a number of recent studies on translesion synthesis by RNA polymerases resulting in the production of mutant transcripts (transcriptional mutagenesis). Over a dozen different types of DNA damage are now known to be bypassed with various degrees of efficiency and miscoding abilities by the transcriptional elongation machinery. Some important biological implications of transcriptional mutagenesis are discussed.