ArticleThe EMBO journal2025
TERRA R-loops trigger a switch in telomere maintenance towards break-induced replication and PRIMPOL-dependent repair.
Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Kinetic Control of Condensate Function: How the Formation Dynamics of APBs Influence ALT Cancer Telomere Length Heterogeneity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- Epigenetic control of telomeric RNA maintains heterochromatin in telomerase-driven cancers.Signal transduction and targeted therapy · 2026Article
- Orphan nuclear receptors recruit TRIM28 to promote telomeric H3K9me3 for the ALT pathway.The EMBO journal · 2026Article
- Epitranscriptomic control of telomere maintenance.Molecular biology reports · 2026Review
- Tankyrases and Their Binding Proteins: Origins of Their Roles in Diverse Cellular Pathways.Cells · 2026Review
- Article
- Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells.Cell reports · 2025Article
- Possible role of human ribonuclease dicer in the regulation of R loops.FEBS open bio · 2025Review
- The DNA damage tolerance factor Rad5 and telomere replication.Current genetics · 2025Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
TERRA long noncoding RNAs associate with telomeres post transcription through base-pairing with telomeric DNA forming R-loop structures. TERRA regulates telomere maintenance but its exact modes of action remain unknown. Here, we induce TERRA transcription and R-loop formation in telomerase-expressing cells and determine that TERRA R-loop formation requires non-redundant functions of the RAD51 DNA recombinase and its enhancer RAD51AP1. TERRA R-loops interfere with semiconservative DNA replication, promoting telomere maintenance by a homology-directed repair (HDR) mechanism known as break-induced replication (BIR), which ensures telomere maintenance in ALT cancer cells. In addition, TERRA induces PRIMPOL-dependent repair, which can initiate DNA synthesis de novo downstream of replication obstacles. PRIMPOL acts in parallel to BIR for telomere maintenance of TERRA-overexpressing cells, promoting their survival. Similarly, we find that PRIMPOL depletion is synthetic-lethal with BIR deficiency in U2OS ALT cancer cells. Therefore, TERRA R-loops by themselves are sufficient to induce ALT-typical telomere repair mechanisms, in the absence of other ALT-typical telomeric chromatin changes.
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