Linking UV-induced DNA damage with base pair sequences
Ultraviolet (UV) radiation induces DNA damage associated with cancer and aging, yet the sequence dependence of UV absorption remains to be investigated. Here, we present a systematic study of the UV absorption spectra of DNA based on all-electron Hartree-Fock calculations. We analyze all possible sequences up to four base pairs, as well as longer randomized sequences and genomic nullomers - motifs which are missing in a given genome. We observe a pronounced sequence dependence: cytosine- and guanine-rich motifs exhibit significantly enhanced absorption, whereas adenine-thymine-rich sequences absorb up to four times less in the mid-UV range. Notably, the human genome is biased toward adenine-thymine-rich sequences, giving it an increased susceptibility to UV-induced damage. In addition, we introduce a computational framework enabling spectral calculations of large DNA and RNA fragments, opening the door to large-scale optical analyses.