{"doi":"10.1093/nar/gkab591","title":"Single molecule analysis indicates stimulation of MUTYH by UV-DDB through enzyme turnover","abstract":"The oxidative base damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is a highly mutagenic lesion because replicative DNA polymerases insert adenine (A) opposite 8-oxoG. In mammalian cells, the removal of A incorporated across from 8-oxoG is mediated by the glycosylase MUTYH during base excision repair (BER). After A excision, MUTYH binds avidly to the abasic site and is thus product inhibited. We have previously reported that UV-DDB plays a non-canonical role in BER during the removal of 8-oxoG by 8-oxoG glycosylase, OGG1 and presented preliminary data that UV-DDB can also increase MUTYH activity. In this present study we examine the mechanism of how UV-DDB stimulates MUTYH. Bulk kinetic assays show that UV-DDB can stimulate the turnover rate of MUTYH excision of A across from 8-oxoG by 4-5-fold. Electrophoretic mobility shift assays and atomic force microscopy suggest transient complex formation between MUTYH and UV-DDB, which displaces MUTYH from abasic sites. Using single molecule fluorescence analysis of MUTYH bound to abasic sites, we show that UV-DDB interacts directly with MUTYH and increases the mobility and dissociation rate of MUTYH. UV-DDB decreases MUTYH half-life on abasic sites in DNA from 8800 to 590 seconds. Together these data suggest that UV-DDB facilitates productive turnover of MUTYH at abasic sites during 8-oxoG:A repair.","journal":"Nucleic Acids Research","year":2021,"id":161201,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"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":506060,"name":"Matthew A. Schaich","orcid":"0000-0001-6771-5623","position":1,"is_corresponding":false},{"id":675554,"name":"Cindy Khuu","orcid":"0000-0002-9144-0137","position":2,"is_corresponding":false},{"id":676201,"name":"Brittani L Schnable","orcid":null,"position":3,"is_corresponding":false},{"id":675555,"name":"Chandrima Majumdar","orcid":"0000-0002-6000-536X","position":4,"is_corresponding":false},{"id":631229,"name":"Simon C Watkins","orcid":null,"position":5,"is_corresponding":false},{"id":379467,"name":"Sheila S. David","orcid":"0000-0001-5873-7935","position":6,"is_corresponding":false},{"id":182885,"name":"Bennett Van Houten","orcid":"0000-0002-4009-2478","position":7,"is_corresponding":false},{"id":399928,"name":"Sunbok Jang","orcid":"0000-0001-7371-0124","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:44:52.299342Z","pmid":"34232996","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":[]}