Contrasting structural impacts induced by cis-syn cyclobutane dimer and (6-4) adduct in DNA duplex decamers: implication in mutagenesis and repair activity

Photochem Photobiol. 1995 Jul;62(1):44-50. doi: 10.1111/j.1751-1097.1995.tb05236.x.


The relative biological importance of cis--syn cyclobutane dimer and pyrimidine(6-4)pyrimidone photoadduct ([6-4] photoadduct) appears to be dependent on the biological species, dipyrimidine sites and local conformational variation induced at the damaged sites. The single-strained deoxynucleotide 10-mers containing the site-specific (6-4) adduct or cis--syn cyclobutane dimer of thymidylyl(3'-->5')-thymidine were generated by direct photolysis of d(CGCATTACGC) with UVC (220-260 nm) irradiation or UVB (260-320 nm) photosensitization. Three-dimensional structures of the duplex cis--syn and (6-4) decamers of d(CGCATTACGC)xd(GCGTAATGCG) were determined by NMR spectroscopy and the relaxation matrix refinement method. The NMR data and structural calculations establish that Watson-Crick base pairing is still intact at the cis--syn dimer site while the hydrogen bonding is absent at the 3'-side of the (6-4) lesion where the T-->C transition mutation is predominantly targeted. Overall conformation of the duplex cis--syn decamer was B-DNA and produced a 9 degree bending in the DNA helix, but a distinctive base orientation of the (6-4) lesion provided a structural basis leading to 44 degree helical bending. The observed local structure and conformational rigidity at the (6-4) adduct of the thymidylyl(3'-5')-thymidine (T-T [6-4]) lesion site suggest the potential absence of hydrogen bonding at the 3' sides of the (6-4) lesion with a substituted nucleotide during replication under SOS conditions. Contrasting structural distortions induced ny the T-T (6-4) adduct with respect to the T-T cis--syn cyclobutane pyrimidine photodimer may explain the large differences in mutation spectrum and repair activities between them.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Adducts*
  • DNA Repair*
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Molecular Structure
  • Mutagenesis*
  • Nucleic Acid Conformation
  • Pyrimidine Dimers / chemistry*


  • DNA Adducts
  • Pyrimidine Dimers