eprintid: 1351727 rev_number: 46 eprint_status: archive userid: 608 dir: disk0/01/35/17/27 datestamp: 2012-07-03 23:21:11 lastmod: 2020-02-13 05:45:02 status_changed: 2012-07-24 09:24:46 type: article metadata_visibility: show item_issues_count: 0 creators_name: Davies, RJH creators_name: Malone, JF creators_name: Gan, Y creators_name: Cardin, CJ creators_name: Lee, MPH creators_name: Neidle, S title: High-resolution crystal structure of the intramolecular d(TpA) thymine-adenine photoadduct and its mechanistic implications ispublished: pub divisions: UCL divisions: A01 divisions: B02 divisions: C08 divisions: D10 note: © 2007 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: A high-resolution crystal structure is reported for d(TpA)*, the intramolecular thymine–adenine photoadduct that is produced by direct ultraviolet excitation of the dinucleoside monophosphate d(TpA). It confirms the presence of a central 1,3-diazacyclooctatriene ring linking the remnants of the T and A bases, as previously deduced from heteronuclear NMR measurements by Zhao et al. (The structure of d(TpA)*, the major photoproduct of thymidylyl-(3′-5′)-deoxyadenosine. Nucleic Acids Res., 1996, 24, 1554–1560). Within the crystal, the d(TpA)* molecules exist as zwitterions with a protonated amidine fragment of the eight-membered ring neutralizing the charge of the internucleotide phosphate monoanion. The absolute configuration at the original thymine C5 and C6 atoms is determined as 5S,6R. This is consistent with d(TpA)* arising by valence isomerization of a precursor cyclobutane photoproduct with cis–syn stereochemistry that is generated by [2 + 2] photoaddition of the thymine 5,6-double bond across the C6 and C5 positions of adenine. This mode of photoaddition should be favoured by the stacked conformation of adjacent T and A bases in B-form DNA. It is probable that the primary photoreaction is mechanistically analogous to pyrimidine dimerization despite having a much lower quantum yield. date: 2007-01-30 id_number: PubMed ID: 17264133 official_url: http://dx.doi.org./10.1093/nar/gkl1101 vfaculties: VFLS oa_status: green language: eng primo: open primo_central: open_green verified: verified_manual elements_source: WoS-Lite elements_id: 418314 doi: 10.1093/nar/gkl1101 lyricists_name: Neidle, Stephen lyricists_id: SNEID18 full_text_status: public publication: NUCLEIC ACIDS RESEARCH volume: 35 number: 4 pagerange: 1048 - 1053 issn: 0305-1048 citation: Davies, RJH; Malone, JF; Gan, Y; Cardin, CJ; Lee, MPH; Neidle, S; (2007) High-resolution crystal structure of the intramolecular d(TpA) thymine-adenine photoadduct and its mechanistic implications. NUCLEIC ACIDS RESEARCH , 35 (4) 1048 - 1053. 10.1093/nar/gkl1101 <https://doi.org/10.1093/nar%2Fgkl1101>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1351727/1/gkl1101.pdf