DNA Polymerase ζ Drives RNA-DNA Recombination

DNA double-strand breaks (DSBs) are dangerous lesions threatening genomic stability. Fidelity of DSB repair is best achieved by recombination with a homologous template sequence. In yeast, transcript RNA was shown to template DSB repair of chromosomal DNA. However, molecular pathways of RNA-driven repair processes remain obscure. Utilizing assays of RNA-DNA recombination with and without an induced DSB in yeast DNA, we reveal a major role of translesion DNA polymerase ζ in DSB repair by RNA. Moreover, Pol ζ catalytic subunit Rev3 with Rev1 and Rad5 are essential for RNA-templated DNA modification with no DSB. Contrary to RNA-templated DNA repair and modification, DSB repair templated by RNA copied into DNA (cDNA) is dependent on the reverse transcriptase activity of the yeast retrotransposon, and clippases Rad1-10/Msh2-3. This study characterizes mechanisms of RNA-DNA recombination, uncovering a new role of Pol ζ in transferring genetic information from RNA to DNA.