{"doi":"10.1093/nar/gkab041","title":"Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs","abstract":"We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.","journal":"Nucleic Acids Research","year":2021,"id":187185,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"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":746713,"name":"Lane Smith","orcid":null,"position":1,"is_corresponding":false},{"id":746714,"name":"Callie Johnson","orcid":null,"position":2,"is_corresponding":false},{"id":746715,"name":"Alyssa Richey","orcid":null,"position":3,"is_corresponding":false},{"id":746716,"name":"Makayla Berry","orcid":null,"position":4,"is_corresponding":false},{"id":746198,"name":"Jessica H. Hartman","orcid":"0000-0002-9134-7469","position":5,"is_corresponding":false},{"id":570636,"name":"Leena Maddukuri","orcid":null,"position":6,"is_corresponding":false},{"id":570240,"name":"Megan R. Reed","orcid":"0000-0001-5086-7938","position":7,"is_corresponding":false},{"id":746199,"name":"Julie Gunderson","orcid":"0000-0003-0219-4390","position":8,"is_corresponding":false},{"id":385347,"name":"Justin Leung","orcid":"0000-0003-4601-390X","position":9,"is_corresponding":false},{"id":391330,"name":"Robert L. Eoff","orcid":"0000-0003-4776-8925","position":10,"is_corresponding":false},{"id":570241,"name":"Amit Ketkar","orcid":"0000-0002-6536-7415","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:48:51.315888Z","pmid":"33555350","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":[]}