{"doi":"10.1101/2020.07.27.222380","title":"NBS1-CtIP–Mediated DNA End Resection Regulates cGAS Binding to Micronuclei","abstract":"Abstract Cyclic GMP-AMP synthase (cGAS), an important component of immune signaling, is hyperactivated in cells defective for DNA damage response (DDR) signaling. However, a direct role for DDR factors in the regulation of cGAS functions is mostly unknown. Here, we provide novel evidence that Nijmegen breakage syndrome 1 (NBS1) protein, a well-studied DNA double-strand break (DSB) sensor, in coordination with ATM, a protein kinase, and CtBP-interacting protein (CtIP), a DNA end resection factor, functions as an upstream regulator of cGAS binding to micronuclei. Upon NBS1 binding to micronuclei via its fork-head–associated domain, it recruits ATM and CtIP via its N- and C-terminal domains, respectively. Subsequently, ATM stabilizes NBS1’s interaction with micronuclei, and CtIP converts DSB ends into single-strand DNA ends, and these two key events preclude cGAS from binding to micronuclei. Notably, we show that purified cGAS cannot form a complex with DNA substrates that mimic resected DNA ends in vitro. Thus, NBS1 together with its binding partners modify the chromatin architecture of the micronuclei and that plays a critical role in cGAS’s binding to micronuclei.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123905,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":290499,"name":"Shibani Mukherjee","orcid":null,"position":1,"is_corresponding":false},{"id":567529,"name":"Souparno Bhattacharya","orcid":"0000-0002-8681-6363","position":2,"is_corresponding":false},{"id":290500,"name":"Debapriya Sinha","orcid":null,"position":3,"is_corresponding":false},{"id":289439,"name":"Sharda Kumari","orcid":"0000-0001-5864-5475","position":4,"is_corresponding":false},{"id":240355,"name":"Hesham A. Sadek","orcid":"0000-0002-4745-366X","position":5,"is_corresponding":false},{"id":241114,"name":"Janice Ortega","orcid":"0000-0002-1193-0532","position":6,"is_corresponding":false},{"id":4790,"name":"Guo-Min Li","orcid":null,"position":7,"is_corresponding":false},{"id":240347,"name":"Aroumougame Asaithamby","orcid":"0000-0001-5195-4224","position":8,"is_corresponding":false},{"id":240346,"name":"Salim Abdisalaam","orcid":"0000-0002-6466-9833","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","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":[]}