Accessibility navigation


High-resolution crystal structure of the intramolecular d(TpA) thymine-adenine photoadduct and its mechanistic implications

Davies, R.J.H., Malone, J.F., Gan, Y., Cardin, C.J., Lee, M.P.H. and Neidle, S. (2007) High-resolution crystal structure of the intramolecular d(TpA) thymine-adenine photoadduct and its mechanistic implications. Nucleic Acids Research, 35 (4). pp. 1048-1053. ISSN 0305-1048

Full text not archived in this repository.

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1093/nar/gkl1101

Abstract/Summary

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.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
ID Code:11181
Uncontrolled Keywords:CYCLOBUTANE PYRIMIDINE DIMERS, EXCITED-STATE DYNAMICS, ULTRAVIOLET-RADIATION, MAJOR PHOTOPRODUCT, INDUCED MUTATIONS, DNA, SEQUENCE, REPAIR, CELLS, RNA

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation