TY - JOUR AV - public Y1 - 2007/01/30/ VL - 35 SP - 1048 EP - 1053 TI - High-resolution crystal structure of the intramolecular d(TpA) thymine-adenine photoadduct and its mechanistic implications IS - 4 N1 - © 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. UR - http://dx.doi.org./10.1093/nar/gkl1101 SN - 0305-1048 N2 - 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. ID - discovery1351727 A1 - Davies, RJH A1 - Malone, JF A1 - Gan, Y A1 - Cardin, CJ A1 - Lee, MPH A1 - Neidle, S JF - NUCLEIC ACIDS RESEARCH ER -