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- Title
R-Loops in Genome Instability and Cancer.
- Authors
Li, Fang; Zafar, Alyan; Luo, Liang; Denning, Ariana Maria; Gu, Jun; Bennett, Ansley; Yuan, Fenghua; Zhang, Yanbin
- Abstract
Simple Summary: R-loops are three-stranded structures consisting of an RNA–DNA hybrid and an unpaired single-stranded DNA (ssDNA), with biological implications in cellular physiology and pathological conditions. R-loops interfere with DNA repair pathways and activate oncogenes, leading to dysregulated cell proliferation, genome instability, and cancer development. R-loops accumulate in several types of cancer cells, including breast, ovarian, prostate, and lung cancer. Studying the biological roles of R-loops in cancer development is potentially beneficial for innovative diagnostic and treatment approaches for cancer. In this review, we focus on recent advances in R-loops' roles in genome instability, DNA repair, and oncogenic events. R-loops are unique, three-stranded nucleic acid structures that primarily form when an RNA molecule displaces one DNA strand and anneals to the complementary DNA strand in a double-stranded DNA molecule. R-loop formation can occur during natural processes, such as transcription, in which the nascent RNA molecule remains hybridized with the template DNA strand, while the non-template DNA strand is displaced. However, R-loops can also arise due to many non-natural processes, including DNA damage, dysregulation of RNA degradation pathways, and defects in RNA processing. Despite their prevalence throughout the whole genome, R-loops are predominantly found in actively transcribed gene regions, enabling R-loops to serve seemingly controversial roles. On one hand, the pathological accumulation of R-loops contributes to genome instability, a hallmark of cancer development that plays a role in tumorigenesis, cancer progression, and therapeutic resistance. On the other hand, R-loops play critical roles in regulating essential processes, such as gene expression, chromatin organization, class-switch recombination, mitochondrial DNA replication, and DNA repair. In this review, we summarize discoveries related to the formation, suppression, and removal of R-loops and their influence on genome instability, DNA repair, and oncogenic events. We have also discussed therapeutical opportunities by targeting pathological R-loops.
- Subjects
TUMOR genetics; TUMOR diagnosis; TUMOR treatment; GENETIC mutation; DNA; CARCINOGENESIS; ONCOGENES; RNA; MEDICAL technology; NEOPLASTIC cell transformation; CELL proliferation; TUMORS
- Publication
Cancers, 2023, Vol 15, Issue 20, p4986
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers15204986