Photosensitized [2 + 2] cycloaddition of N-acetylated cytosine affords stereoselective formation of cyclobutane pyrimidine dimer.
Photocycloaddition between two adjacent bases in DNA produces a cyclobutane pyrimidine dimer (CPD), which is one of the major UV-induced DNA lesions, with either the cis-syn or trans-syn structure. In this study, we investigated the photosensitized intramolecular cycloaddition of partially-protected thymidylyl-(3'→5')-N(4)-acetyl-2'-deoxy-5-methylcytidine, to clarify the effect of the base modification on the cycloaddition reaction. The reaction resulted in the stereoselective formation of the trans-syn CPD, followed by hydrolysis of the acetylamino group. The same result was obtained for the photocycloaddition of thymidylyl-(3'→5')-N(4)-acetyl-2'-deoxycytidine, whereas both the cis-syn and trans-syn CPDs were formed from thymidylyl-(3'→5')-thymidine. Kinetic analyses revealed that the activation energy of the acid-catalyzed hydrolysis is comparable to that reported for the thymine-cytosine CPD. These findings provided a new strategy for the synthesis of oligonucleotides containing the trans-syn CPD. Using the synthesized oligonucleotide, translesion synthesis by human DNA polymerase η was analyzed.
Yamamoto
Junpei
J
Division of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
Nishiguchi
Kosuke
K
Manabe
Koichiro
K
Masutani
Chikahide
C
Hanaoka
Fumio
F
Iwai
Shigenori
S
D044503:5-Methylcytosine / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D009841:Oligonucleotides / Q000096:biosynthesis / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D055668:Photochemical Processes; D011740:Pyrimidine Dimers / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature; D013941:Thymine / Q000737:chemistry; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D044503:5-Methylcytosine; D004259:DNA-Directed DNA Polymerase; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D011740:Pyrimidine Dimers; D013941:Thymine; C434331:phosphoramidite; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases