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Linear Amplification Mediated PCR – Localization of Genetic Elements and Characterization of Unknown Flanking DNA
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R-loops as a trigger for intra- and extrachromosomal DNA amplification in cancer.
Tatyana F Kovalenko1, Amal Abdurazakov1, Nadezhda V Antipova1,2
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
Frontiers in Cell and Developmental Biology
|December 19, 2025
Summary
R-loops, DNA:RNA hybrids, are crucial for normal cell functions but can cause DNA damage and genomic instability when dysregulated. Their role in initiating gene amplification in cancer, particularly extrachromosomal DNA (ecDNA), is increasingly evident.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- R-loops are DNA:RNA hybrids that play vital roles in normal cellular processes like replication and DNA repair.
- Aberrant R-loop formation can lead to DNA damage, genomic instability, and replicative collapse.
- Extrachromosomal DNA (ecDNA) amplification is a hallmark of cancer malignancy, driving tumor evolution and therapy resistance.
Purpose of the Study:
- To review the multifaceted role of R-loops in DNA damage and repair.
- To explore the connection between R-loops and gene amplification, especially ecDNA formation in cancer.
- To discuss potential R-loop involvement in yet-undemonstrated amplification mechanisms.
Main Methods:
- Literature review focusing on R-loop biology and cancer genomics.
- Analysis of existing evidence linking R-loops to DNA damage and genomic instability.
- Examination of gene amplification events potentially induced by R-loops.
Main Results:
- R-loops are implicated in replicative collapse, double-strand breaks, and DNA damage repair pathways.
- Upregulated transcription, potentially leading to R-loop formation, increases susceptibility to gene amplification.
- Specific examples of R-loop-induced gene amplifications are presented.
Conclusions:
- R-loops are critical mediators of DNA damage and genomic instability.
- R-loops likely play a significant role in initiating gene amplification, contributing to cancer progression.
- Further research is warranted to elucidate the full extent of R-loop involvement in cancer genome evolution.
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