ArticleMolecular cell2022
TERRA and RAD51AP1 promote alternative lengthening of telomeres through an R- to D-loop switch.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- 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
- Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.Aging cell · 2026Review
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- G-quadruplex homeostasis is a determinant of PARP inhibitor toxicity in BRCA2-deficient cells.Nature communications · 2026Article
- G quadruplex DNA facilitates a pervasive path to homologous recombination.bioRxiv : the preprint server for biology · 2026Article
- R-PLA enables enhanced detection of R-loops in mammalian cells using proximity ligation.Cell reports methods · 2026Article
- TRF2-RAP1 inhibits homology-directed repair of telomeres by promoting BLM-mediated removal of telomere R-loops.Nucleic acids research · 2026Article
- Structural organization and function of telomeric chromatin.Nature cell biology · 2026Review
- The High-Throughput C-Circle Assay for Identifying Modulators of Alternative Lengthening of Telomeres(ALT) Activity.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.Research (Washington, D.C.) · 2026Review
- Transcriptional regulation of telomeric repeat-containing RNA by the G-quadruplex-binding Ewing sarcoma protein.Scientific reports · 2025Article
- RAD51AP1 is a versatile RAD51 modulator.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The alternative lengthening of telomeres pathway through a DNA repair lens: mechanism and therapeutic opportunities.NAR cancer · 2025Review
- Modulating TERRA G-quadruplexes with ligands: impact on telomeric DNA:RNA hybrids and ALT mechanisms.Nucleic acids research · 2025Article
- Break-induced replication is activated to repair R-loop-associated double-strand breaks in SETX-deficient cells.Cell reports · 2025Article
- Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms.BMC genomics · 2025Article
- Mechanisms and genomic implications of break-induced replication.Nature structural & molecular biology · 2025Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alternative lengthening of telomeres (ALT), a telomerase-independent process maintaining telomeres, is mediated by break-induced replication (BIR). RAD52 promotes ALT by facilitating D-loop formation, but ALT also occurs through a RAD52-independent BIR pathway. Here, we show that the telomere non-coding RNA TERRA forms dynamic telomeric R-loops and contributes to ALT activity in RAD52 knockout cells. TERRA forms R-loops in vitro and at telomeres in a RAD51AP1-dependent manner. The formation of R-loops by TERRA increases G-quadruplexes (G4s) at telomeres. G4 stabilization enhances ALT even when TERRA is depleted, suggesting that G4s act downstream of R-loops to promote BIR. In vitro, the telomeric R-loops assembled by TERRA and RAD51AP1 generate G4s, which persist after R-loop resolution and allow formation of telomeric D-loops without RAD52. Thus, the dynamic telomeric R-loops formed by TERRA and RAD51AP1 enable the RAD52-independent ALT pathway, and G4s orchestrate an R- to D-loop switch at telomeres to stimulate BIR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.