{"doi":"10.1016/j.celrep.2022.111448","title":"Molecular basis for processing of topoisomerase 1-triggered DNA damage by Apn2/APE2","abstract":"Topoisomerase 1 (Top1) incises DNA containing ribonucleotides to generate complex DNA lesions that are resolved by APE2 (Apn2 in yeast). How Apn2 engages and processes this DNA damage is unclear. Here, we report X-ray crystal structures and biochemical analysis of Apn2-DNA complexes to demonstrate how Apn2 frays and cleaves 3' DNA termini via a wedging mechanism that facilitates 1-6 nucleotide endonucleolytic cleavages. APN2 deletion and DNA-wedge mutant Saccharomyces cerevisiae strains display mutator phenotypes, cell growth defects, and sensitivity to genotoxic stress in a ribonucleotide excision repair (RER)-defective background harboring a high density of Top1-incised ribonucleotides. Our data implicate a wedge-and-cut mechanism underpinning the broad-specificity Apn2 nuclease activity that mitigates mutagenic and genome instability phenotypes caused by Top1 incision at genomic ribonucleotides incorporated by DNA polymerase epsilon.","journal":"Cell Reports","year":2022,"id":284085,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"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":271492,"name":"Jessica L. Wojtaszek","orcid":"0000-0002-9108-2886","position":1,"is_corresponding":false},{"id":961846,"name":"Denise C. Appel","orcid":null,"position":2,"is_corresponding":false},{"id":398021,"name":"J.M. Krahn","orcid":"0000-0002-4640-0267","position":3,"is_corresponding":false},{"id":245442,"name":"Bret D. Wallace","orcid":"0000-0002-9107-5045","position":4,"is_corresponding":false},{"id":961358,"name":"Evan Walsh","orcid":"0000-0002-1180-4755","position":5,"is_corresponding":false},{"id":73052,"name":"Thomas A. Kunkel","orcid":"0000-0002-9900-1788","position":6,"is_corresponding":false},{"id":225589,"name":"R. Scott Williams","orcid":"0000-0002-4610-8397","position":7,"is_corresponding":false},{"id":598764,"name":"Jessica S. Williams","orcid":"0000-0002-9758-5812","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T00:29:32.702533Z","pmid":"36198268","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":[]}