Rosa Luna1,2, Belén Gómez-González1,2 and Andrés Aguilera1,2 1Andalusian Center of Molecular Biology and Regenerative Medicine (CABIMER), Universidad de Sevilla-Spanish National Research Council (CSIC), 41092 Seville, Spain; 2Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain Corresponding author: aguilous.es Abstract

Genome integrity relies on the accuracy of DNA metabolism, but as appreciated for more than four decades, transcription enhances mutation and recombination frequencies. More recent research provided evidence for a previously unforeseen link between RNA and DNA metabolism, which is often related to the accumulation of DNA–RNA hybrids and R-loops. In addition to physiological roles, R-loops interfere with DNA replication and repair, providing a molecular scenario for the origin of genome instability. Here, we review current knowledge on the multiple RNA factors that prevent or resolve R-loops and consequent transcription–replication conflicts and thus act as modulators of genome dynamics.