{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:17:59Z","timestamp":1787894279699,"version":"build-2784847793"},"reference-count":38,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01\u2010ES023350"],"award-info":[{"award-number":["R01\u2010ES023350"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:p>\n                    Anticancer nitrogen mustard drugs including cyclophosphamide, mechlorethamine and chlorambucil induce covalent DNA\u2013protein cross\u2010links (DPCs) by sequentially alkylating the N7 position of guanine in DNA and amino acid residues within proteins. In cells, DPCs are proteolytically processed to yield corresponding peptide\u2010DNA cross\u2010links (DpCs), allowing polymerase bypass. In this study, site\u2010specific, hydrolytically stable DNA lesions resembling nitrogen mustard\u2010induced DpCs were generated via oxime ligation of an 11\u2010mer peptide derived from histone H4 (NH\n                    <jats:sub>2<\/jats:sub>\n                    \u2013GGGK*GLGKGGA, K*=oxy\u2010lysine) to 7\u2010deaza\u20107\u2010(2,3\u2010dihydroprop\u20101\u2010yl)\u2010dG (DHP) in DNA. DNA sequence was derived from codon 249 of the\n                    <jats:italic>p53<\/jats:italic>\n                    tumor suppressor gene, a common mutational hotspot in tumors. Translesion synthesis (TLS) experiments of DpC containing plasmids in human HEK 293T cells revealed that 7\u2010deaza\u2010DpC lesion was bypassed most efficiently in wild\u2010type cells (83%) with lower efficiency in Pol \u03b9 KO (53%), Pol \u03b7 KO (59%), and Pol \u03ba KO (63%) cells, with Pol \u03b6 KO unaffected (76%). Mutation frequency for polymerase bypass of 7\u2010deaza\u2010DpC (~9%) was significantly higher than for 7\u2010deaza\u2010DHP\u2010dG control (~5%). Pol \u03b7 and Pol \u03b9 knockouts led to increased error rates, suggesting they play a role in error\u2010free bypass of DpCs. In contrast Pol \u03b6 deficiency reduced mutation rates, implying that it plays a role in error\u2010prone bypass.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70507","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:34:22Z","timestamp":1787312062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DNA\u2013Peptide Crosslinks Placed at Codon 249 of the\n                    <i>p53<\/i>\n                    Tumor Suppressor Gene Induce G to A Transitions in Human Cells"],"prefix":"10.1002","volume":"27","author":[{"given":"Priscilla","family":"Yawson","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9780-7438","authenticated-orcid":false,"given":"Jan Henric T.","family":"Bacurio","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honnaiah Vijay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and the Masonic Cancer Center University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0621-6860","authenticated-orcid":false,"given":"Natalia Y.","family":"Tretyakova","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and the Masonic Cancer Center University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7951-4984","authenticated-orcid":false,"given":"Ashis K.","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.053"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-06705-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2005.06.039"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c09293"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2010.12.007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad860"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.745257"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb5001795"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.5c00215"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202109418"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00034-08"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062917-012405"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3289"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010363"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2147"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001008"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.08.028"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/350427a0"},{"key":"e_1_2_9_20_1","first-page":"6358","article-title":"p53 Gene Mutation Spectrum in Hepatocellular Carcinoma","volume":"52","author":"Oda T.","year":"1992","journal-title":"Cancer Research"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20495"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx049774"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2021.09.005"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CC01300D"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.105786"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky444"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.21.8001-8007.2000"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.6b00397"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.3893"},{"key":"e_1_2_9_30_1","first-page":"2070","article-title":"Carcinogens Preferentially Bind at Methylated CpG in the p53 Mutational Hot Spots","volume":"58","author":"Chen J. X.","year":"1998","journal-title":"Cancer Research"},{"key":"e_1_2_9_31_1","first-page":"1987","article-title":"Prevalence and Spectrum of p53 Mutations Associated With Smoking in Breast Cancer","volume":"62","author":"Conway K.","year":"2002","journal-title":"Cancer Research"},{"key":"e_1_2_9_32_1","first-page":"2432","article-title":"Synthesis of a Homologous Series of Side Chain Extended Orthogonally\u2010Protected Aminooxy\u2010Containing Amino Acids","volume":"15","author":"Liu F.","year":"2008","journal-title":"Synthesis"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc400018u"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801238200"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.1c00130"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.56"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo061037q"},{"key":"e_1_2_9_38_1","first-page":"9256","article-title":"Translesion Synthesis of O4\u2010Alkylthymidine Lesions in Human Cells","volume":"44","author":"Wu J.","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.003477"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70507","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.70507","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:37:20Z","timestamp":1787891840000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.70507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":38,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8,27]]}},"alternative-id":["10.1002\/cbic.70507"],"URL":"https:\/\/doi.org\/10.1002\/cbic.70507","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"assertion":[{"value":"2026-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70507"}}