Direct Observation of Structural Dynamics in the Dimerization of DNA Base Pairs via Time-Resolved X-ray Solution Scattering

The UV-induced formation of lesions in DNA has intrigued scientists since its first observation in 1958. Thymine (T), cytosine (C), and uracil (U) undergo photodimerization upon UV irradiation, disrupting complementary bonds and damaging the double helix. While this process follows a [2+2] cycloaddition, its kinetics and mechanism remain debated. Here, we investigate the structural dynamics of UV-induced dimerization in solvated pyrimidine nucleobases using time-resolved X-ray liquidography (TRXL). As no structure-sensitive probe has directly captured this process, our study will offer unprecedented insights into nucleobase evolution before and during photodimerization, advancing our understanding of DNA lesion formation and repair.