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They are activated in the liver to give reactive nitrenium ions that react with nucleobases within the DNA duplex. The reaction occurs predominantly at the C8 position of the dG base, thereby giving C8\u2010acetyl\u2010aryl\u2010 or C8\u2010aryl\u2010dG adducts in an electrophilic aromatic substitution reaction. Alternatively, reaction with the exocyclic 2\u2010NH<jats:sub>2<\/jats:sub> group is observed. Although the C8 adducts retain base\u2010pairing properties, base pairing is strongly compromised in the case of the <jats:italic>N<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup> adducts. Here we show crystal structures of two DNA lesions, <jats:italic>N<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>\u2010acetylnaphthyl\u2010dG and C8\u2010fluorenyl\u2010dG, within a DNA duplex recognized by the repair protein Rad14. The structures confirm that two molecules of the repair protein recognize the lesion and induce a 72 or 78\u00b0 kink at the site of the damage. Importantly, the same overall kinked structure is induced by binding of the repair proteins, although the structurally different lesions result in distinct stacking interactions of the lesions within the duplex. The results suggest that the repair protein XPA\/Rad14 is a sensor that recognizes flexibility. The protein converts the information that structurally different lesions are present in the duplex into a unifying sharply kinked recognition motif.<\/jats:p>","DOI":"10.1002\/cbic.201700169","type":"journal-article","created":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T09:23:26Z","timestamp":1493198606000},"page":"1379-1382","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structural Insights into the Recognition of <i>N<\/i><sup><i>2<\/i><\/sup>\u2010Aryl\u2010 and C8\u2010Aryl DNA Lesions by the Repair Protein XPA\/Rad14"],"prefix":"10.1002","volume":"18","author":[{"given":"Charlotte","family":"Ebert","sequence":"first","affiliation":[{"name":"Center for Integrated Protein Science at the Department of Chemistry Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen  Butenandtstrasse 5\u201313 81377 M\u00fcnchen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Simon","sequence":"additional","affiliation":[{"name":"Center for Integrated Protein Science at the Department of Chemistry Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen  Butenandtstrasse 5\u201313 81377 M\u00fcnchen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1054-8689","authenticated-orcid":false,"given":"Sabine","family":"Schneider","sequence":"additional","affiliation":[{"name":"Center for Integrated Protein Science at the Department of Chemistry Technische Universit\u00e4t M\u00fcnchen  Lichtenbergstrasse 4 85748 Garching Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-2831","authenticated-orcid":false,"given":"Thomas","family":"Carell","sequence":"additional","affiliation":[{"name":"Center for Integrated Protein Science at the Department of Chemistry Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen  Butenandtstrasse 5\u201313 81377 M\u00fcnchen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,5,30]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","first-page":"559","volume":"30","author":"Miller J. 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