{"doi":"10.1016/j.celrep.2021.109879","title":"RNF168 E3 ligase participates in ubiquitin signaling and recruitment of SLX4 during DNA crosslink repair","abstract":"SLX4/FANCP is a key Fanconi anemia (FA) protein and a DNA repair scaffold for incision around a DNA interstrand crosslink (ICL) by its partner XPF nuclease. The tandem UBZ4 ubiquitin-binding domains of SLX4 are critical for the recruitment of SLX4 to damage sites, likely by binding to K63-linked polyubiquitin chains. However, the identity of the ubiquitin E3 ligase that mediates SLX4 recruitment remains unknown. Using small interfering RNA (siRNA) screening with a GFP-tagged N-terminal half of SLX4 (termed SLX4-N), we identify the RNF168 E3 ligase as a critical factor for mitomycin C (MMC)-induced SLX4 foci formation. RNF168 and GFP-SLX4-N colocalize in MMC-induced ubiquitin foci. Accumulation of SLX4-N at psoralen-laser ICL tracks or of endogenous SLX4 at Digoxigenin-psoralen/UVA ICL is dependent on RNF168. Finally, we find that RNF168 is epistatic with SLX4 in promoting MMC tolerance. We conclude that RNF168 is a critical component of the signal transduction that recruits SLX4 to ICL damage.","journal":"Cell Reports","year":2021,"id":192416,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":759476,"name":"Masako Abe","orcid":"0000-0002-9675-9817","position":1,"is_corresponding":false},{"id":760178,"name":"Seon Young Park","orcid":null,"position":2,"is_corresponding":false},{"id":759477,"name":"Wenwen Wu","orcid":"0000-0002-3654-585X","position":3,"is_corresponding":false},{"id":759478,"name":"Hiromasa Yabe","orcid":"0000-0001-6508-5496","position":4,"is_corresponding":false},{"id":759479,"name":"Miharu Yabe","orcid":"0000-0003-0697-5506","position":5,"is_corresponding":false},{"id":74281,"name":"Haico van Attikum","orcid":"0000-0001-8590-0240","position":6,"is_corresponding":false},{"id":759480,"name":"Shinichiro Nakada","orcid":"0000-0001-9297-1565","position":7,"is_corresponding":false},{"id":759481,"name":"Tomohiko Ohta","orcid":"0000-0002-9700-7342","position":8,"is_corresponding":false},{"id":447872,"name":"Michael M. Seidman","orcid":"0000-0001-5718-5016","position":9,"is_corresponding":false},{"id":759482,"name":"Yonghwan Kim","orcid":"0000-0001-8574-4938","position":10,"is_corresponding":false},{"id":610829,"name":"Minoru Takata","orcid":"0000-0002-4926-3675","position":11,"is_corresponding":false},{"id":759475,"name":"Y Katsuki","orcid":"0000-0002-2549-7426","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:49:43.496702Z","pmid":"34706224","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":[]}