{"doi":"10.1093/nar/gkae105","title":"DNA-PK controls Apollo’s access to leading-end telomeres","abstract":"The complex formed by Ku70/80 and DNA-PKcs (DNA-PK) promotes the synapsis and the joining of double strand breaks (DSBs) during canonical non-homologous end joining (c-NHEJ). In c-NHEJ during V(D)J recombination, DNA-PK promotes the processing of the ends and the opening of the DNA hairpins by recruiting and/or activating the nuclease Artemis/DCLRE1C/SNM1C. Paradoxically, DNA-PK is also required to prevent the fusions of newly replicated leading-end telomeres. Here, we describe the role for DNA-PK in controlling Apollo/DCLRE1B/SNM1B, the nuclease that resects leading-end telomeres. We show that the telomeric function of Apollo requires DNA-PKcs's kinase activity and the binding of Apollo to DNA-PK. Furthermore, AlphaFold-Multimer predicts that Apollo's nuclease domain has extensive additional interactions with DNA-PKcs, and comparison to the cryo-EM structure of Artemis bound to DNA-PK phosphorylated on the ABCDE/Thr2609 cluster suggests that DNA-PK can similarly grant Apollo access to the DNA end. In agreement, the telomeric function of DNA-PK requires the ABCDE/Thr2609 cluster. These data reveal that resection of leading-end telomeres is regulated by DNA-PK through its binding to Apollo and its (auto)phosphorylation-dependent positioning of Apollo at the DNA end, analogous but not identical to DNA-PK dependent regulation of Artemis at hairpins.","journal":"Nucleic Acids Research","year":2024,"id":429977,"datarank":0.7117040475822594,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.24804767957851184,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.24804767957851184,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":16,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":true,"deposit_databanks":{"figshare":["10.6084/m9.figshare.25028588"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1036151,"name":"Beatrice Toia","orcid":"0000-0003-0451-1839","position":1,"is_corresponding":false},{"id":1232621,"name":"Patrik Eickhoff","orcid":"0009-0004-1926-7706","position":2,"is_corresponding":false},{"id":1036673,"name":"Andreea M. Matei","orcid":null,"position":3,"is_corresponding":false},{"id":1232977,"name":"Michael El Beyrouthy","orcid":null,"position":4,"is_corresponding":false},{"id":1232622,"name":"Björn Wallner","orcid":"0000-0002-3772-8279","position":5,"is_corresponding":false},{"id":1232623,"name":"Max E. Douglas","orcid":"0000-0003-1186-7163","position":6,"is_corresponding":false},{"id":250641,"name":"Titia de Lange","orcid":"0000-0002-9267-367X","position":7,"is_corresponding":false},{"id":1036153,"name":"Francisca Lottersberger","orcid":"0000-0002-0677-8986","position":8,"is_corresponding":false},{"id":1232620,"name":"Ceylan Sönmez","orcid":"0000-0001-5763-7625","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T01:59:11.328802Z","pmid":"38407308","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}