The structure of d(TpA), the major photoproduct of thymidylyl-(3'5')- deoxyadenosine

Abstract

Irradiation of the dinucleotide TpdA and TA-containing oligonucleotides and DNA produces the TA* photoproduct which was proposed to be the [2+2] cyclo-addition adduct between the C5-C6 double bonds of the T and the A [Bose,S.N., Kumar,S., Davies,R.J.H., Sethi,S.K. and McCloskey,J.A. (1984) Nucleic Acids Res. 12, 7929-7947]. The proposed structure was based on a variety of spectroscopic and chemical degradation studies, and the assignment of a trans-syn-I stereochemistry was based on an extensive 1H-NMR and molecular modeling study of the dinucleotide adduct [Koning,T.M.G., Davies,R.J.H. and Kaptein,R. (1990) Nucleic Acids Res. 18, 277-284]. However, a number of properties of TA* are not in accord with the originally proposed structure, and prompted a re-evaluation of the structure. To assign the 13C spectrum and establish the bond connectivities of the TA* photoproduct of TpdA [d(TpA)*], 1H-13C heteronuclear multiple-quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC) spectra were obtained. The 13C shifts and connectivities were found to be inconsistent with the originally proposed cyclobutane ring fusion between the thymine and adenine, but could be explained by a subsequent ring-expansion reaction to give an eight-membered ring valence isomer. The new structure for the d(TpA)* resolves the inconsistencies with the originally proposed structure, and could have a stereochemistry that arises from the anti, anti glycosyl conformation found in B form DNA.

RNA Is More UV Resistant than DNA: The Formation of UV‐Induced DNA Lesions is Strongly Sequence and Conformation Dependent

“…For hairpin 4, we observed in the HPLC-MS (followed by ion extraction), formation of new peaks with only very small intensity. More detailed analysis of these peaks by HPLC-MS/MS showed that the peaks are formed by dApdT photoproducts, in accordance with previous observations by Zhao et al [70] In contrast, hairpins 5-7 are efficiently degraded by UVC light in comparison to hairpins 1-4. Figure 2 shows the HPLC profiles of all three hairpins before (bottom) and after (top) irradiation.…”

Photocrosslinking of human telomeric G-quadruplex loops by anti cyclobutane thymine dimer formation

“…We also detected a small amount of the TA* photoproduct (peak 2) (Fig. S3B) (28,29). HPLC peaks 7 and 8 were both assigned as Fig.…”

Purines as targets for DNA photodamage

“…It was originally inferred from spectroscopic analysis to incorporate a cyclobutane ring linking the C-5 and C-6 atoms of thymine to C-6 and C-5 of adenine respectively [ 16,171. More recently, evidence derived from I3C NMR strongly suggests [18] that it exists as a less strained valence isomer of this structure (see Figure 1). Sensitive detection of TA* in UV-irradiated DNA is possible because acid hydrolysis converts it specifically into the intensely fluorescent heterocyclic base 6-methylimidazo[4,5-b]pyridin-5-one ( formation of the parent photoproduct TA* [19].…”