Bridging the gap: R-loop mediated genomic instability and its implications in neurological diseases.

ABSTRACT

R-loops, intricate three-stranded structures formed by RNA-DNA hybrids and an exposed non-template DNA strand, are fundamental to various biological phenomena. They carry out essential and contrasting functions within cellular mechanisms, underlining their critical role in maintaining cellular homeostasis. The specific cellular context that dictates R-loop formation determines their function, particularly emphasizing the necessity for their meticulous genomic regulation. Notably, the aberrant formation or misregulation of R-loops is implicated in numerous neurological disorders. This review focuses on the complex interactions between R-loops and double-strand DNA breaks, exploring how R-loop dysregulation potentially contributes to the pathogenesis of various brain disorders, which could provide novel insights into the molecular mechanisms underpinning neurological disease progression and identify potential therapeutic targets by highlighting these aspects.

R-loops are special structures inside our cells, made when a piece of RNA (a molecule similar to DNA) sticks to DNA, exposing a part of the DNA. These structures play important roles in how our cells work, helping to keep them healthy and functioning properly. However, when these R-loops do not form correctly or are not controlled well by the cell, they can cause problems. This is especially true in the brain, where mistakes in R-loop formation can lead to various neurological disorders, which are conditions that affect the brain and nerves. In our review, we examine how R-loops interact with certain types of DNA damage and how this can lead to brain disorders. We hope that by understanding these interactions better, scientists can find new ways to treat or prevent these conditions.