The paradox of R-loops: guardians of the genome or drivers of disease?
Abstract
R-loops, chromatin structures containing DNA–RNA hybrids with displaced single-stranded DNA, play crucial roles in various cellular processes. Their formation is influenced by factors such as DNA topology, RNA stability, and the presence of GC-rich regions. However, excessive or uncontrolled R-loop accumulation can threaten genomic stability, leading to DNA damage, particularly double-strand breaks. To preserve genome integrity, cells have developed mechanisms to regulate R-loop formation and resolution. Dysregulation of these processes is linked to several diseases, including cancer and neurodegenerative disorders. In this review, we will explore the dynamics of R-loop formation and resolution and how they are detected, their roles in DNA damage and repair, and how their dysregulation may lead to immune responses and disease pathogenesis.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
