ArticleEMBO reports2023
An AlphaFold2 map of the 53BP1 pathway identifies a direct SHLD3-RIF1 interaction critical for shieldin activity.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026Review
- Deciphering protein mutation-phenotype linkages from CRISPR-based tiling mutagenesis screens.Cell systems · 2026Article
- 53BP1-independent Shieldin-BRCA1 antagonism at replication-coupled double-strand breaks.Nature communications · 2026Article
- Double strand breaks drive toxicity in a Huntington's disease mouse model with or without somatic expansion.Nature communications · 2026Article
- DNA-damage dependent isoform switching modulates RIF1 DNA repair complex assembly and phase separation.The Journal of biological chemistry · 2025Article
- Proteome-widebioRxiv : the preprint server for biology · 2025Article
- Selective disruption of DNMT1/ELK1 interactions induces DGKI re-expression and promotes temozolomide sensitivity of MGMTClinical epigenetics · 2025Article
- CRAMP1-dependent histone H1 biogenesis is essential for topoisomerase II inhibitor tolerance.Molecular cell · 2025Article
- Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion.bioRxiv : the preprint server for biology · 2025Article
- Cooperative role of PACT and ADAR1 in preventing aberrant PKR activation by self-derived double-stranded RNA.Nature communications · 2025Article
- Emerging frontiers in protein structure prediction following the AlphaFold revolution.Journal of the Royal Society, Interface · 2025Review
- Predictomes, a classifier-curated database of AlphaFold-modeled protein-protein interactions.Molecular cell · 2025Article
- Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain.Nature communications · 2024Article
- AlphaFold two years on: Validation and impact.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cyclin F-EXO1 axis controls cell cycle-dependent execution of double-strand break repair.Science advances · 2024Article
- NFATC2IP is a mediator of SUMO-dependent genome integrity.Genes & development · 2024Article
- Predictomes: A classifier-curated database of AlphaFold-modeled protein-protein interactions.bioRxiv : the preprint server for biology · 2024Article
- Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024Review
- Interrogation and validation of the interactome of neuronal Munc18-interacting Mint proteins with AlphaFold2.The Journal of biological chemistry · 2024Article
- An AlphaFold2 map of the 53BP1 pathway identifies a direct SHLD3-RIF1 interaction critical for shieldin activity.EMBO reports · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
53BP1 is a chromatin-binding protein that promotes DNA double-strand break repair through the recruitment of downstream effectors including RIF1, shieldin, and CST. The structural basis of the protein-protein interactions within the 53BP1-RIF1-shieldin-CST pathway that are essential for its DNA repair activity is largely unknown. Here, we used AlphaFold2-Multimer (AF2) to predict all possible pairwise combinations of proteins within this pathway and provide structural models of seven previously characterized interactions. This analysis also predicted an entirely novel binding interface between the HEAT-repeat domain of RIF1 and the eIF4E-like domain of SHLD3. Extensive interrogation of this interface through both in vitro pulldown analysis and cellular assays supports the AF2-predicted model and demonstrates that RIF1-SHLD3 binding is essential for shieldin recruitment to sites of DNA damage, and for its role in antibody class switch recombination and PARP inhibitor sensitivity. Direct physical interaction between RIF1 and SHLD3 is therefore essential for 53BP1-RIF1-shieldin-CST pathway activity.
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Registered trials
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.