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

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.

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Publication Details

Journal
Cancer Science
Published
2025-11-24
DOI
https://doi.org/10.1111/cas.70272
Primary Topic
DNA Repair Mechanisms
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Keiko Shinjo, Miho Suzuki, Tatsunori Nishimura, Yutaka Kondo
Cancer Science
DNA Repair Mechanisms
article

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

Keiko Shinjo, Miho Suzuki, Tatsunori Nishimura, Yutaka Kondo
article en

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.

Cancer ScienceVol. 117(2)
Aichi Cancer Center (JP), Nagoya University (JP)
Japan Society for the Promotion of Science
Openalex Percentile: Top 68%
DNA Repair Mechanisms
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