{"corpus_id":19541319,"paper_sha":"9c9334303958617df25835217461c1919cd1f399","doi":"10.1074/jbc.M608876200","arxiv_id":null,"pmid":17138560,"pmcid":"PMC1941669","mag_id":2061126697,"dblp_id":null,"acl_id":null,"title":"Interactions of Human O6-Alkylguanine-DNA Alkyltransferase (AGT) with Short Single-stranded DNAs*","year":2007,"publication_date":"2007-02-02","venue":"Journal of Biological Chemistry","journal":{"name":"Journal of Biological Chemistry","pages":"3357 - 3366","volume":"282"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural"],"s2_fields_of_study":["Biology","Medicine","Chemistry"],"reference_count":59,"citation_count":46,"influential_citation_count":2,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Base Sequence","mj":false,"ui":"D001483"},{"d":"DNA, Single-Stranded","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D004277"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Kinetics","mj":false,"ui":"D007700"},{"d":"Molecular Sequence Data","mj":false,"ui":"D008969"},{"d":"O(6)-Methylguanine-DNA Methyltransferase","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D019853"},{"d":"Oligodeoxyribonucleotides","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D009838"},{"d":"Polydeoxyribonucleotides","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D011089"},{"d":"Protein Binding","mj":false,"ui":"D011485"},{"d":"Recombinant Proteins","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D011994"},{"d":"Substrate Specificity","mj":false,"ui":"D013379"}],"chemicals":[{"n":"DNA, Single-Stranded","ui":"D004277","reg":"0"},{"n":"Oligodeoxyribonucleotides","ui":"D009838","reg":"0"},{"n":"Polydeoxyribonucleotides","ui":"D011089","reg":"0"},{"n":"Recombinant Proteins","ui":"D011994","reg":"0"},{"n":"O(6)-Methylguanine-DNA Methyltransferase","ui":"D019853","reg":"EC 2.1.1.63"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.jbc.org/article/S0021925818384217/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/9c9334303958617df25835217461c1919cd1f399","s2_open_access_license":"CCBY","s2_open_access_status":"HYBRID","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"The O6-alkylguanine-DNA alkyltransferase (AGT) repairs O6-alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. Here we characterize the binding of AGT to single-stranded DNAs ranging in length from 5 to 78 nucleotides (nt). Binding is moderately cooperative (37.9 ± 3.0 ≤ ω ≤ 89.8 ± 8.9), resulting in an all-or-nothing association pattern on short templates. This cooperativity contrasts with the isolated binding seen in recent crystal structures of AGT-DNA complexes. The statistical binding site size S (mean = 5.2 ± 0.1) oscillates with increasing template length. The oscillation period (4.10 ± 0.02 nt/protein) is nearly identical to the binding site size obtained at the highest known binding density (S = 4 nt/protein) and is significantly smaller than the contour length (∼8 bp) occupied in crystalline complexes. A model in which AGT proteins overlap along the DNA contour is proposed to account for these features. Oscillations in intrinsic binding constant Ki and cooperativity factor ω have the same frequency but are of opposite phase to S with the result that the most stable protein-protein and protein-DNA interactions occur at the highest packing densities. We hypothesize that modest binding cooperativity and high binding densities are adaptations that allow AGT to efficiently search for lesions in the context of chromatin remodeling and DNA replication.","claims":[{"public_id":"cl_6cef1f646ccb7fbde28c618aa6c32576","status":"active","text":"An overlapping-protein model along the DNA contour accounts for the observed binding-site oscillations and packing-dependent interaction features.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_6cef1f646ccb7fbde28c618aa6c32576"},{"public_id":"cl_4e6ab8cfa56bd7d3852161e25255d36b","status":"active","text":"Binding of human O6-alkylguanine-DNA alkyltransferase to short single-stranded DNAs is moderately cooperative, producing an all-or-nothing association pattern on short templates.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_4e6ab8cfa56bd7d3852161e25255d36b"},{"public_id":"cl_728dd8c6705c6c37bb026e8e5f15e566","status":"active","text":"Intrinsic binding constant Ki and cooperativity factor ω oscillate with the same frequency but opposite phase to binding site size, so the strongest protein-protein and protein-DNA interactions occur at the highest packing densities.","confidence":0.93,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_728dd8c6705c6c37bb026e8e5f15e566"},{"public_id":"cl_7774123f0414562b4185b42f12867bee","status":"active","text":"The statistical binding site size oscillates with increasing single-stranded DNA template length, with an average site size of 5.2 ± 0.1 nucleotides per protein and a period of 4.10 ± 0.02 nucleotides per protein.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_7774123f0414562b4185b42f12867bee"}],"concepts":[{"public_id":"co_1ef2e96d756a1c6f614d8e30518b2d31","status":"active","name":"overlapping protein model","description":"A binding model in which adjacent AGT proteins overlap along the DNA contour.","types":["model"],"aliases":["overlap model"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_1ef2e96d756a1c6f614d8e30518b2d31"},{"public_id":"co_253d121b4674e13b544ddd0c39ece839","status":"active","name":"human O6-alkylguanine-DNA alkyltransferase","description":"A human DNA repair 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path traced by the DNA backbone along which proteins are positioned.","types":["structural property"],"aliases":["DNA contour length"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_3b40f96464d49ffc9e06d860e2c05303"},{"public_id":"co_7e31450589c0d4fc4d5773daea2732be","status":"active","name":"statistical binding site size","description":"The average number of nucleotides occupied per bound AGT protein on the DNA template.","types":["binding parameter"],"aliases":["S"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_7e31450589c0d4fc4d5773daea2732be"},{"public_id":"co_92d73dc4ab64de94bfb1adcf7516e2be","status":"active","name":"binding site oscillations","description":"Periodic changes in AGT 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