ArticleNature structural & molecular biology2023
DNA-PK and the TRF2 iDDR inhibit MRN-initiated resection at leading-end telomeres.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Fission yeast RPA-TERT-Tpz1TPP1 complex promotes telomere extension and suppresses telomere recombination.PLoS genetics · 2026Article
- Fission yeast RPA-TERT-Tpz1bioRxiv : the preprint server for biology · 2026Article
- Quantifying telomere length: from bulk assays to single-molecule resolution.Biophysics reports · 2026Article
- Rap1-mediated steric hindrance protects telomeres from MRX sensing.Nature structural & molecular biology · 2026Article
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- Phage-encoded TelN inhibits bacterial Mre11-Rad50 nuclease to protect hairpin telomeres.The EMBO journal · 2025Article
- TRF1 and TRF2 form distinct shelterin subcomplexes at telomeres.Cell reports · 2025Article
- Structural basis for DNA break sensing by human MRE11-RAD50-NBS1 and its regulation by telomeric factor TRF2.Nature communications · 2025Article
- Using the safety scissors: DNA resection regulation at DNA double-strand breaks and telomeres.DNA repair · 2025Review
- Mechanisms and regulation of DNA end resection in the maintenance of genome stability.Nature reviews. Molecular cell biology · 2025Review
- Restriction of Ku translocation protects telomere ends.Nature communications · 2025Article
- Article
- Multimeric protein interaction and complex prediction: Structure, dynamics and function.Computational and structural biotechnology journal · 2025Review
- Functional and molecular insights into the role of Sae2 C-terminus in the activation of MRX endonuclease.Nucleic acids research · 2024Article
- Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres.Nucleic acids research · 2024Article
- DNA-PK controls Apollo's access to leading-end telomeres.Nucleic acids research · 2024Article
- Ccq1 restrains Mre11-mediated degradation to distinguish short telomeres from double-strand breaks.Nucleic acids research · 2024Article
- Rif2 interaction with Rad50 counteracts Tel1 functions in checkpoint signalling and DNA tethering by releasing Tel1 from MRX binding.Nucleic acids research · 2024Article
- All roads lead to MRN regulation at telomeres: different paths to one solution.Nature structural & molecular biology · 2023Article
- SMC-based immunity against extrachromosomal DNA elements.Biochemical Society transactions · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Telomeres replicated by leading-strand synthesis lack the 3' overhang required for telomere protection. Surprisingly, resection of these blunt telomeres is initiated by the telomere-specific 5' exonuclease Apollo rather than the Mre11-Rad50-Nbs1 (MRN) complex, the nuclease that acts at DNA breaks. Without Apollo, leading-end telomeres undergo fusion, which, as demonstrated here, is mediated by alternative end joining. Here, we show that DNA-PK and TRF2 coordinate the repression of MRN at blunt mouse telomeres. DNA-PK represses an MRN-dependent long-range resection, while the endonuclease activity of MRN-CtIP, which could cleave DNA-PK off of blunt telomere ends, is inhibited in vitro and in vivo by the iDDR of TRF2. AlphaFold-Multimer predicts a conserved association of the iDDR with Rad50, potentially interfering with CtIP binding and MRN endonuclease activation. We propose that repression of MRN-mediated resection is a conserved aspect of telomere maintenance and represents an ancient feature of DNA-PK and the iDDR.
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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.