{"doi":"10.3389/fmolb.2022.808036","title":"Human Mitochondrial DNA Polymerase Metal Dependent UV Lesion Bypassing Ability","abstract":"Human mitochondrial DNA contains more UV-induced lesions than the nuclear DNA due to lack of mechanism to remove bulky photoproducts. Human DNA polymerase gamma (Pol γ) is the sole DNA replicase in mitochondria, which contains a polymerase ( pol ) and an exonuclease ( exo ) active site. Previous studies showed that Pol γ only displays UV lesion bypassing when its exonuclease activity is obliterated. To investigate the reaction environment on Pol γ translesion activity, we tested Pol γ DNA activity in the presence of different metal ions. While Pol γ is unable to replicate through UV lesions on DNA templates in the presence of Mg 2+ , it exhibits robust translesion DNA synthesis (TLS) on cyclobutane pyrimidine dimer (CPD)-containing template when Mg 2+ was mixed with or completely replaced by Mn 2+ . Under these conditions, the efficiency of Pol γ′s TLS opposite CPD is near to that on a non-damaged template and is 800-fold higher than that of exonuclease-deficient Pol γ. Interestingly, Pol γ exhibits higher exonuclease activity in the presence of Mn 2+ than with Mg 2+ , suggesting Mn 2+ -stimulated Pol γ TLS is not via suppressing its exonuclease activity. We suggest that Mn 2+ ion expands Pol γ′s pol active site relative to Mg 2+ so that a UV lesion can be accommodated and blocks the communication between pol and exo active sites to execute translesion DNA synthesis.","journal":"Frontiers in Molecular Biosciences","year":2022,"id":278510,"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":0.9548,"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":951089,"name":"Noe Baruch‐Torres","orcid":"0000-0002-0978-7570","position":1,"is_corresponding":false},{"id":483353,"name":"Shigenori Iwai","orcid":"0000-0002-7873-937X","position":2,"is_corresponding":false},{"id":582667,"name":"Geoffrey K. Herrmann","orcid":"0000-0002-0581-616X","position":3,"is_corresponding":false},{"id":951090,"name":"Luis G. Brieba","orcid":"0000-0002-6073-5207","position":4,"is_corresponding":false},{"id":469532,"name":"Y. Whitney Yin","orcid":"0000-0001-7063-9385","position":5,"is_corresponding":false},{"id":877675,"name":"Joon Park","orcid":"0000-0002-3983-6433","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T00:28:47.357993Z","pmid":"35355510","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":[]}