Photosensitized [2 + 2] cycloaddition of N-acetylated cytosine affords stereoselective formation of cyclobutane pyrimidine dimer

Nucleic Acids Res. 2011 Feb;39(3):1165-75. doi: 10.1093/nar/gkq855. Epub 2010 Sep 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / chemistry
  • DNA-Directed DNA Polymerase / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Oligonucleotides / biosynthesis
  • Oligonucleotides / chemistry
  • Organophosphorus Compounds / chemistry
  • Photochemical Processes
  • Pyrimidine Dimers / chemical synthesis
  • Pyrimidine Dimers / chemistry*
  • Stereoisomerism
  • Temperature
  • Thymine / chemistry
  • Ultraviolet Rays


  • Oligonucleotides
  • Organophosphorus Compounds
  • Pyrimidine Dimers
  • phosphoramidite
  • 5-Methylcytosine
  • DNA-Directed DNA Polymerase
  • Rad30 protein
  • Thymine