{"doi":"10.1128/jvi.43.2.679-686.1982","title":"Resistance of Adenoviral DNA Replication to Aphidicolin Is Dependent on the 72-Kilodalton DNA-Binding Protein","abstract":"<jats:p>\n            Aphidicolin is a highly specific inhibitor of DNA polymerase α and has been most useful for assessing the role of this enzyme in various replication processes (J. A. Huberman, Cell\n            <jats:bold>23</jats:bold>\n            :647-648, 1981). Both nuclear DNA replication and simian virus 40 DNA replication are highly sensitive to this drug (Krokan et al., Biochemistry\n            <jats:bold>18</jats:bold>\n            :4431-4443, 1979), whereas mitochondrial DNA synthesis is completely insensitive (Zimmerman et al., J. Biol. Chem.\n            <jats:bold>255</jats:bold>\n            :11847-11852, 1980). Adenovirus DNA replication is sensitive to aphidicolin, but only at much higher concentrations. These patterns of sensitivity are seen both in vivo and in vitro (Krokan et al., Biochemistry\n            <jats:bold>18</jats:bold>\n            :4431-4443, 1979). A temperature-sensitive mutant of adenovirus type 5 known as H5\n            <jats:italic>ts</jats:italic>\n            125 is able to complete but not initiate new rounds of replication at nonpermissive temperatures (P. C. van der Vliet and J. S. Sussenbach, Virology\n            <jats:bold>67</jats:bold>\n            :415-426, 1975). When cells infected with H5\n            <jats:italic>ts</jats:italic>\n            125 were shifted from permissive (33°C) to nonpermissive (41°C) conditions, the residual DNA synthesis (elongation) showed a striking increase in sensitivity to aphidicolin. The temperature-sensitive mutation of H5\n            <jats:italic>ts</jats:italic>\n            125 is in the gene for the 72-kilodalton single-stranded DNA-binding protein. This demonstrated that the increased resistance to aphidicolin shown by adenovirus DNA replication was dependent on that protein. It also supports an elongation role for both DNA polymerase α and the 72-kilodalton single-stranded DNA-binding protein in adenovirus DNA replication. Further support for an elongation role of DNA polymerase α came from experiments with permissive temperature conditions and inhibiting levels of aphidicolin in which it was shown that newly initiated strands failed to elongate to completion.\n          </jats:p>","journal":"Journal of Virology","year":1982,"id":678997,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1774062,"name":"Petros Hantzopoulos","orcid":null,"position":1,"is_corresponding":false},{"id":115417,"name":"Geoffrey Zubay","orcid":null,"position":2,"is_corresponding":false},{"id":152239,"name":"David A. Foster","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Resistance of Adenoviral DNA Replication to Aphidicolin Is Dependent on the 72-Kilodalton DNA-Binding Protein","abstract":"<jats:p>\n            Aphidicolin is a highly specific inhibitor of DNA polymerase α and has been most useful for assessing the role of this enzyme in various replication processes (J. A. Huberman, Cell\n            <jats:bold>23</jats:bold>\n            :647-648, 1981). Both nuclear DNA replication and simian virus 40 DNA replication are highly sensitive to this drug (Krokan et al., Biochemistry\n            <jats:bold>18</jats:bold>\n            :4431-4443, 1979), whereas mitochondrial DNA synthesis is completely insensitive (Zimmerman et al., J. Biol. Chem.\n            <jats:bold>255</jats:bold>\n            :11847-11852, 1980). Adenovirus DNA replication is sensitive to aphidicolin, but only at much higher concentrations. These patterns of sensitivity are seen both in vivo and in vitro (Krokan et al., Biochemistry\n            <jats:bold>18</jats:bold>\n            :4431-4443, 1979). A temperature-sensitive mutant of adenovirus type 5 known as H5\n            <jats:italic>ts</jats:italic>\n            125 is able to complete but not initiate new rounds of replication at nonpermissive temperatures (P. C. van der Vliet and J. S. Sussenbach, Virology\n            <jats:bold>67</jats:bold>\n            :415-426, 1975). When cells infected with H5\n            <jats:italic>ts</jats:italic>\n            125 were shifted from permissive (33°C) to nonpermissive (41°C) conditions, the residual DNA synthesis (elongation) showed a striking increase in sensitivity to aphidicolin. The temperature-sensitive mutation of H5\n            <jats:italic>ts</jats:italic>\n            125 is in the gene for the 72-kilodalton single-stranded DNA-binding protein. This demonstrated that the increased resistance to aphidicolin shown by adenovirus DNA replication was dependent on that protein. It also supports an elongation role for both DNA polymerase α and the 72-kilodalton single-stranded DNA-binding protein in adenovirus DNA replication. Further support for an elongation role of DNA polymerase α came from experiments with permissive temperature conditions and inhibiting levels of aphidicolin in which it was shown that newly initiated strands failed to elongate to completion.\n          </jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"6809958","pmcid":"PMC256170","openalex_id":"https://openalex.org/W1508297454","authors":[],"funders":[],"total_grants":0,"fwci":1.8767,"citation_percentile":0.85687259,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://jvi.asm.org/content/jvi/43/2/679.full.pdf","host_type":"journal"},{"url":"https://jvi.asm.org/content/jvi/43/2/679.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/jvi.43.2.679-686.1982","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.43.2.679-686.1982","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/6809958","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC256170","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/256170","host_type":"repository"}],"fields_of_study":["Virus-based gene therapy research","CRISPR and Genetic Engineering","DNA Repair Mechanisms","Adenoviruses, Human","Aphidicolin","Carrier Proteins","Cell Line","DNA Replication","DNA, Viral","DNA-Binding Proteins","Diterpenes","Drug Resistance, Microbial","Humans","Mutation","Temperature","Virus Replication"],"mesh_terms":["Adenoviruses, Human","Carrier Proteins","Cell Line","Diterpenes","DNA Replication","DNA-Binding Proteins","DNA, Viral","Drug Resistance, Microbial","Humans","Mutation","Temperature","Virus Replication","Aphidicolin"],"keywords":["Aphidicolin","Biology","DNA replication","Replication factor C","Molecular biology","DNA polymerase II","DNA polymerase","DNA polymerase delta","Replication protein A","Eukaryotic DNA replication","Control of chromosome duplication","DNA clamp","DNA","DNA-binding protein","Biochemistry","Gene","Reverse transcriptase","Polymerase chain reaction"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T11:59:39.857812Z","pmid":null,"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":[]}