ArticleScientific reports2019
FANCM suppresses DNA replication stress at ALT telomeres by disrupting TERRA R-loops.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- Distinct functions of mammalian RAD51 paralogs in genome maintenance.Biochemical Society transactions · 2026Review
- Beyond End Protection: Shelterin, POT1 Dysfunction, and Telomere Replication Stress in Cancer.Biomolecules · 2026Review
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- SLX4IP limits replication stress globally and at ALT telomeres.The EMBO journal · 2026Article
- Highly mutagenic copying of telomeric circles promotes ALT establishment.Nature communications · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Local heterochromatin enrichment promotes telomere clustering and PML nuclear body assembly at telomeres.Cell reports · 2026Article
- The PARP1-EXD2 axis orchestrates R-loop resolution to safeguard genome stability.Nature chemical biology · 2026Article
- Structural organization and function of telomeric chromatin.Nature cell biology · 2026Review
- The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts.Nucleic acids research · 2026Article
- Association of Hypertension With Telomere Length, Considering Non-Genetic and Genetic Factors, in Middle-Aged Koreans.Journal of clinical hypertension (Greenwich, Conn.) · 2025Article
- Optical pooled screening for the discovery of regulators of the alternative lengthening of telomeres pathway.Methods (San Diego, Calif.) · 2025Article
- Genetic mapping and isolation of Rht28, a locus on wheat chromosome arm 2AL affecting plant height, grain size, and grain weight.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2025Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Distinct mechanisms underlying extrachromosomal telomere DNA generation in ALT cancers.Nucleic acids research · 2025Article
- Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells.eLife · 2025Article
- TRF1 relies on fork reversal to prevent fragility at human telomeres.Nature communications · 2025Article
- R-loops: a key driver of inflammatory responses in cancer.Experimental & molecular medicine · 2025Review
- Targeting FANCM by antisense oligonucleotides in ALT-positive cancers.Molecular therapy. Nucleic acids · 2025Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells maintain their telomeres by either re-activating telomerase or adopting the homologous recombination (HR)-based Alternative Lengthening of Telomere (ALT) pathway. Among the many prominent features of ALT cells, C-circles (CC) formation is considered to be the most specific and quantifiable biomarker of ALT. However, the molecular mechanism behind the initiation and maintenance of CC formation in ALT cells is still largely unknown. We reported previously that depletion of the FANCM complex (FANCM-FAAP24-MHF1&2) in ALT cells induced pronounced replication stress, which primarily takes place at their telomeres. Here, we characterized the changes in ALT associated phenotypes in cells deficient of the FANCM complex. We found that depletion of FAAP24 or FANCM, but not MHF1&2, induces a dramatic increase of CC formation. Most importantly, we identified multiple DNA damage response (DDR) and DNA repair pathways that stimulate the dramatic increase of CC formation in FANCM deficient cells, including the dissolvase complex (BLM-TOP3A-RMI1/2, or BTR), DNA damage checkpoint kinases (ATR and Chk1), HR proteins (BRCA2, PALB2, and Rad51), as well as proteins involved in Break-Induced Replication (BIR) (POLD1 and POLD3). In addition, FANCD2, another Fanconi Anemia (FA) protein, is also required for CC formation, likely through promoting the recruitment of BLM to the replication stressed ALT telomeres. Finally, we demonstrated that TERRA R-loops accumulate at telomeres in FANCM deficient ALT cells and downregulation of which attenuates the ALT-associated PML bodies (APBs), replication stress and CC formation. Taken together, our data suggest that FANCM prevents replisomes from stalling/collapsing at ALT telomeres by disrupting TERRA R-loops.
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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.