title: Transcript RNA supports precise repair of its own DNA gene.
abstract: The transfer of genetic information from RNA to DNA is considered an extraordinary process in molecular biology. Despite the fact that cells transcribe abundant amount of RNA with a wide range of functions, it has been difficult to uncover whether RNA can serve as a template for DNA repair and recombination. An increasing number of experimental evidences suggest a direct role of RNA in DNA modification. Recently, we demonstrated that endogenous transcript RNA can serve as a template to repair a DNA double-strand break (DSB), the most harmful DNA lesion, not only indirectly via formation of a DNA copy (cDNA) intermediate, but also directly in a homology driven mechanism in budding yeast. These results point out that the transfer of genetic information from RNA to DNA is more general than previously thought. We found that transcript RNA is more efficient in repairing a DSB in its own DNA (in cis) than in a homologous but ectopic locus (in trans). Here, we summarize current knowledge about the process of RNA-driven DNA repair and recombination, and provide further data in support of our model of DSB repair by transcript RNA in cis. We show that a DSB is precisely repaired predominately by transcript RNA and not by residual cDNA in conditions in which formation of cDNA by reverse transcription is inhibited. Additionally, we demonstrate that defects in ribonuclease (RNase) H stimulate precise DSB repair by homologous RNA or cDNA sequence, and not by homologous DNA sequence carried on a plasmid. These results highlight an antagonistic role of RNase H in RNA-DNA recombination. Ultimately, we discuss several questions that should be addressed to better understand mechanisms and implications of RNA-templated DNA repair and recombination.
authors.affiliation: a School of Biology, Georgia Institute of Technology , Atlanta , Georgia , USA.
authors.forename: Havva
authors.initials: H
authors.lastname: Keskin
authors.affiliation: a School of Biology, Georgia Institute of Technology , Atlanta , Georgia , USA.
authors.forename: Chance
authors.initials: C
authors.lastname: Meers
authors.affiliation: a School of Biology, Georgia Institute of Technology , Atlanta , Georgia , USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Storici
mesh_terms: D004247:DNA / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics; D012313:RNA / Q000235:genetics*; D011995:Recombination, Genetic; D048348:Reverse Transcription / Q000235:genetics; D016914:Ribonuclease H / Q000235:genetics*
chemical_list: D012313:RNA; D004247:DNA; D016914:Ribonuclease H
keywords: Double-strand break; RNA-templated DNA repair; RNase H; homologous recombination; transcript RNA