Structure and Dynamics of Poly(T) Single-Strand DNA: Implications toward CPD Formation

The formation of cyclobutane pyrimidine dimers between adjacent thymines by UV radiation is thought to be
the first event in a cascade leading to skin cancer. Recent studies showed that thymine dimers are fully
formed within 1 ps of UV irradiation, suggesting that the conformation at the moment of excitation is the
determining factor in whether a given base pair dimerizes. MD simulations on the 50 ns time scale are used
to study the populations of reactive conformers that exist at any given time in T18 single-strand DNA. Trajectory
analysis shows that only a small percentage of the conformations fulfill distance and dihedral requirements
for thymine dimerization, in line with the experimentally observed quantum yield of 3%. Plots of the pairwise
interactions in the structures predict hot spots of DNA damage where dimerization in the ssT18 is predicted
to be most favored. The importance of hairpin formation by intra-strand base pairing for distinguishing reactive
and unreactive base pairs is discussed in detail. The data presented thus explain the structural origin of the
results from the ultrafast studies of thymine dimer formation.