Photoinduced DNA Lesions in Dormant Bacteria: The Peculiar Route Leading to Spore Photoproducts Characterized by Multiscale Molecular Dynamics**

Abstract

Some bacterial species enter a dormant state in the form of spores to resist to unfavorable external conditions. Spores are resistant to a wide series of stress agents, including UV radiation, and can last for tens to hundreds of years. Due to the suspension of biological functions, such as DNA repair, they accumulate DNA damage upon exposure to UV radiation. Differently from active organisms, the most common DNA photoproducts in spores are not cyclobutane pyrimidine dimers, but rather the so‐called spore photoproducts. This noncanonical photochemistry results from the dry state of DNA and its binding to small, acid‐soluble proteins that drastically modify the structure and photoreactivity of the nucleic acid. Herein, multiscale molecular dynamics simulations, including extended classical molecular dynamics and quantum mechanics/molecular mechanics based dynamics, are used to elucidate the coupling of electronic and structural factors that lead to this photochemical outcome. In particular, the well‐described impact of the peculiar DNA environment found in spores on the favored formation of the spore photoproduct, given the small free energy barrier found for this path, is rationalized. Meanwhile, the specific organization of spore DNA precludes the photochemical path that leads to cyclobutane pyrimidine dimer formation.

Photosensitization Reactions of Biomolecules: Definition, Targets and Mechanisms

“…Thus, an efficiently bimolecular quenching rate ( k q = 5.3 × 10 9 m −1 s −1 ) was determined for the reaction of thymidine with DPA in the triplet excited state. In addition, the measured triplet energy ( E at = 328 kJ mol −1 ) for DPA is much higher than that of thymidine thus accrediting the predominance of TTET photosensitized reactions in the overwhelming formation of SP in dry spores (252).…”

A multiscale free energy method reveals an unprecedented photoactivation of a bimetallic Os(ii)–Pt(ii) dual anticancer agent

“…This advanced methodology provides the free energy path of the process simultaneously accounting for both dynamical and environmental effects. 63–65 The Os–Pt photosensitizer 2 was initially solvated inside a cubic water box (Fig. 1).…”

CHAPTER 7. Ultraviolet-induced Formation of DNA Damage in Cells and their Mutational Consequences

“…In contrast to all other living cells, exposure of spores to UV radiation does not lead to the formation of CPDs and 64-PPs but to a dimer involving two adjacent thymine bases, 5-(-thyminyl)-thymine also known as the spore photoproduct (SP) 78 . This specific photochemistry is explained by the unusual A-like form of DNA in spores [79][80][81] . This conformation is induced by the highly dehydrated core environment and the complexation of large amounts of small acid soluble proteins to DNA.…”