Regulation of R‐Loop Dynamics by Proteins and Long Noncoding RNAs : An Emerging Paradigm for Cancer Treatment

ABSTRACT R‐loops are three‐stranded nucleic acid structures comprising an RNA/DNA hybrid and a displaced single‐stranded DNA. While transient R‐loop formation is essential for various physiological processes, their persistent accumulation leads to genomic instability. Cancer cells exhibit elevated R‐loop levels due to hypertranscription, replication stress, and impaired DNA repair pathways. In this review, we provide a comprehensive overview of the molecular machinery that resolves R‐loops, including chromatin remodelers, transcriptional regulators, nucleases, and helicases. We also highlight the emerging roles of long noncoding RNAs (lncRNAs) in modulating R‐loop dynamics and explore how these RNA‐based mechanisms cooperate with canonical resolution pathways. Finally, we explore the potential of targeting R‐loop regulatory networks as a novel therapeutic strategy in cancer treatment.