Solution structure of the DNA decamer duplex containing a 3'-T·T base pair of the cis-syn cyclobutane pyrimidine dimer: implication for the mutagenic property of the cis-syn dimer

Abstract

The cis-syn dimer is the major DNA photoproduct produced by UV irradiation. in order to determine the origin of the mutagenic property of the cis-syn dimer, we used NMR restraints and molecular dynamics to determine the solution structure of a DNA decamer duplex containing a wobble pair between the 3'-T of the cis-syn dimer and the opposite T residue (CS/TA duplex). The solution structure of the CS/TA duplex revealed that the 3'-T T base pair of the cis-syn dimer had base pair geometry that was significantly different from the canonical Watson-Crick base pair and caused destabilization and conformational distortion of its 3'-region. However, a 3'-T A base pair at the cis-syn dimer within this related DNA decamer maintains the normal Watson-Crick base pair geometry and causes little distortion in the conformation of its 3'-side. Our results show that in spite of its stable hydrogen bonding, the insertion of a T residue opposite the 3'-T of the cis-syn dimer is inhibited by structural distortion caused by the 3'-T T base pair. This may explain why the frequency of the 3'-T→A transversion, which is the major mutation produced by the cis-syn dimer, is only 4%.