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However, the same C4\u2032 backbone variants, which by themselves do not perturb complementary hydrogen bonds, induced strong NER reactions when incorporated into short segments of mispaired bases. No oligonucleotide excision was detected when DNA contained abnormal base pairs without concomitant changes in deoxyribose\u2013phosphate composition. Thus, neither C4\u2032 backbone lesions nor improper base pairing stimulated human NER, but the combination of these two substrate alterations constituted an extremely potent signal for double DNA incision. In summary, we used C4\u2032-modified backbone residues as molecular tools to dissect DNA damage recognition by human NER into separate components and identified a bipartite discrimination mechanism that requires changes in DNA chemistry with concurrent disruption of Watson\u2013Crick base pairing.<\/jats:p>","DOI":"10.1073\/pnas.94.13.6664","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"6664-6669","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["Bipartite substrate discrimination by human nucleotide excision\u2009repair"],"prefix":"10.1073","volume":"94","author":[{"given":"Martin T.","family":"Hess","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich\u2013Tierspital, Winterthurerstrasse 260, 8057 Z\u00fcrich, Switzerland; and Institute of Organic Chemistry, University of Basel, St.-Johanns-Ring 19, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Schwitter","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich\u2013Tierspital, Winterthurerstrasse 260, 8057 Z\u00fcrich, Switzerland; and Institute of Organic Chemistry, University of Basel, St.-Johanns-Ring 19, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Petretta","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich\u2013Tierspital, Winterthurerstrasse 260, 8057 Z\u00fcrich, Switzerland; and Institute of Organic Chemistry, University of Basel, St.-Johanns-Ring 19, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Giese","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich\u2013Tierspital, Winterthurerstrasse 260, 8057 Z\u00fcrich, Switzerland; and Institute of Organic Chemistry, University of Basel, St.-Johanns-Ring 19, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanspeter","family":"Naegeli","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Z\u00fcrich\u2013Tierspital, Winterthurerstrasse 260, 8057 Z\u00fcrich, Switzerland; and Institute of Organic Chemistry, University of Basel, St.-Johanns-Ring 19, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,6,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.6.2415"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90289-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1994.01690080084012"},{"key":"e_1_3_3_4_2","first-page":"283","volume-title":"DNA Repair and Mutagenesis","author":"Friedberg E C","year":"1995","unstructured":"E C Friedberg, G C Walker, W Siede DNA Repair and Mutagenesis (Am. 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