Genetic characterization of three distinct mechanisms supporting RNA-driven DNA repair and modification reveals major role of DNA polymerase z

In this study, we explore the molecular pathways involved in RNA-mediated DNA recombination events in yeast Saccharomyces cerevisiae and Saccharomyces paradoxus. We show that cellular endogenous transcript RNA can recombine with homologous DNA with the aid of translesion DNA polymerase z. We discovered a major role of DNA polymerase z in RNA-templated DNA repair of a double-strand break (DSB). This is a novel function of Pol z. Moreover, we uncovered that RNA can modify DNA in a homology driven manner even in the absence of an induced DSB at the homologous DNA site, and this mechanism is completely dependent on Pol z, demonstrating the existence of RNA-DNA recombination events in the absence of an induced DSB.