Photochemistry of cytosine derivatives. 1. Photochemistry of thymidylyl-(3' →5')-deoxycytidine

Abstract

The photochemistry of thymidylyl-(3' leads to 5')- deoxycytidine (dTpdC) was studied as a model system of adjacent thymine and cytosine bases in DNA. Acetophenonesensitized irradiation causes the cytosine moiety in dTpdC to react with the thymine moiety intramolecularly. Three unstable photoproducts are formed initially which are converted into three isomeric dinucleoside phosphates of thymine-uracil cyclobutane photodimer in a ratio of 4.2:2.2:1. Under the same irradiation condition thymidylyl-(3' leads to 5')-thymidine (dTpdT) yields two products in a ratio of 6:1. The structures of these products are established by chemical and spectroscopic methods. The major product in these reactions has been identified as the stereoisomer which has the same anti,anti relationship between the pyrimidine rings and the deoxyribose group as in the parent dinucleoside phosphates. The efficiency of the intramolecular dimerization of dTpdC is about one-third that of dTpdT. The results suggest that the cytosine base in DNA may be converted to a uracil base via photodimerization with an adjacent pyrimidine base, hydrolysis, and photoreactivation.

Two Glycosylase/Abasic Lyases from Neisseria mucosaThat Initiate DNA Repair at Sites of UV-induced Photoproducts

“…This substrate was incubated at 37°C with the indicated enzyme in which 100 mM NaBH 4 had been substituted for the 100 mM NaCl. As a control, duplex 49-mer DNA without a lesion was incubated with the enzyme in the presence of NaBH 4 . A second set of controls contained NaCl (100 mM) in place of NaBH 4 .…”

“…This nucleophile can either be a primary amino group or an activated water molecule (17). If the attacking nucleophile is a primary amino group, a Schiff base intermediate results, which can be reduced by NaBH 4 . This chemical reduction, while the intermediate is still present, will result in a stable covalent linkage between the enzyme and the DNA that can be detected as a shifted band by gel electrophoresis (14,17,31).…”

“…This lesion can exist in two main forms as follows: the cis-syn isomer, which is the predominant form, and the trans-syn isomer, which is less common (3). The trans-syn dimer exists as two stereoisomers, trans-syn I and trans-syn II (4). A defect in the repair of pyrimidine dimers can be associated with several biological consequences, including cell death, mutagenesis, and potentially, carcinogenesis.…”

An NMR and conformational investigation of thetrans-syn cyclobutane photodimers of dUpdT

“…In addition, 3 J U6,T6 values observed for 1b and 2b are similar to those observed for other trans-syn photodimers. 8,9,[11][12][13][14]18 ⌰ 1 values calculated from 3 J U6,T6 , using the Karplus equation, 19 are also consistent with a trans-syn configuration.…”

“…8 -10 Similar investigations of other dinucleoside monophosphates containing the trans-syn cyclobutyl linkage have also appeared. 8,[11][12][13] Furthermore, we have reported an nmr-based conformational analysis of both trans-syn isomers of the cyclobutanetype photoproduct of dTpdU (dT[p]dU).…”