Chemical and biochemical properties of oligonucleotides that contain (5 ' S,6S)-cyclo-5,6-dihydro-2 '-deoxyuridine and (5 ' S,6S)-cyclo-5,6-dihydrothymidine, two main radiation-induced degradation products of pyrimidine 2 '-deoxyribonucleosides

The first chemical synthesis of (5'S,6S)-cyclo-5, 6-dihydro-2'-deoxyuridine [(5' S,6S)-CyclodHdUrd], a major product of gamma irradiation of oxygen fr ee aqueous solution of 2'-deoxycytidine is reported. Subsequently, the latt er cyclonucleoside was incorporated in defined sequence oligodeoxyribunucle otides. The chemical composition of the modified DNA fragments was assessed by enzymatic digestions and mass spectrometry measurements. The latter ana lyses confirmed the presence and the integrity of the lesion within the syn thesised DNA fragments. Replication and repair studies showed that (5'S,6S) -CyclodHdUrd together with (5'S,6S)-CyclodHThd [(5'S,6S)-cyclo-5,6-dihydrot hymidine] inserted into DNA oligomers act as blocks for DNA polymerases and are not excised by DNA N-glycosylases. (C) 2000 Elsevier Science Ltd. All rights reserved.