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. ORCID: https://orcid.org/0000-0002-2556-9995, 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 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
URI	https://reading-clone.eprints-hosting.org/id/eprint/11181
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Uncontrolled Keywords	CYCLOBUTANE PYRIMIDINE DIMERS, EXCITED-STATE DYNAMICS, ULTRAVIOLET-RADIATION, MAJOR PHOTOPRODUCT, INDUCED MUTATIONS, DNA, SEQUENCE, REPAIR, CELLS, RNA
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