{"doi":"10.1101/2022.12.07.519501","title":"Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice","abstract":"Summary The Mre11-Rad50-Nbs1 (MRN) complex recognizes and processes DNA double-strand breaks for homologous recombination by performing short-range removal of 5ʹ strands. Endonucleolytic processing by MRN requires a stably bound protein at the break site—a role we postulate is played by DNA-dependent protein kinase (DNA-PK) in mammals. Here we interrogate the sites of MRN-dependent processing by isolating and sequencing DNA-PK-bound DNA fragments that are products of MRN cleavage. These intermediates are generated with highest efficiency when DNA-PK is catalytically blocked, yielding products within 200 bp of the break site, whereas DNA-PK products in the absence of kinase inhibition show much greater dispersal. Use of light-activated Cas9 to induce breaks facilitates temporal resolution of DNA-PK and Mre11 binding, showing that Mre11 and DNA-PK both bind to DNA ends before release of DNA-PK-bound products. These results support a sequential model of double-strand break repair involving collaborative interactions between homologous and non-homologous repair complexes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302313,"datarank":0.17670162046615337,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.011909777165936926,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.011909777165936926,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":864357,"name":"Alberto Marín-González","orcid":"0000-0002-9076-1270","position":1,"is_corresponding":false},{"id":22168,"name":"Taekjip Ha","orcid":"0000-0003-2195-6258","position":2,"is_corresponding":false},{"id":258487,"name":"Tanya T. Paull","orcid":"0000-0002-2991-651X","position":3,"is_corresponding":false},{"id":258482,"name":"Rajashree A. Deshpande","orcid":"0000-0001-5728-716X","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:16.279991Z","pmid":null,"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":[]}