Multiscale Conformational Sampling Reveals Excited-State Locality in DNA Self-Repair Mechanism

Ultraviolet (UV) irradiation is known
to be responsible for DNA damage. However, experimental studies in
DNA oligonucleotides have shown that UV light can also induce sequence-specific
self-repair. Following charge transfer from a guanine adenine sequence
adjacent to a cyclobutane pyrimidine dimer (CPD), the covalent bond
between the two thymines could be cleaved, recovering the intact base
sequence. Mechanistic details promoting the self-repair remained unclear,
however. In our theoretical study, we investigated whether optical
excitation could directly lead to a charge-transfer state, thereby
initiating the repair, or whether the initial excited state remains
localized on a single nucleobase. We performed conformational sampling
of 200 geometries of the damaged DNA double strand solvated in water
and used a hybrid quantum and molecular mechanics approach to compute
excited states at the complete active space perturbation level of
theory. Analysis of the conformational data set clearly revealed that
the excited-state properties are uniformly distributed across the
fluctuations of the nucleotide in its natural environment. From the
electronic wavefunction, we learned that the electronic transitions
remained predominantly local on either adenine or guanine, and no
direct charge transfer occurred in the experimentally accessed energy
range. The investigated base sequence is not only specific to the
CPD repair mechanism but ubiquitously occurs in nucleic acids. Our
results therefore give a very general insight into the charge locality
of UV-excited DNA, a property that is regarded to have determining
relevance in the structural consequences following absorption of UV
photons.