Theoretical insight into different repair rates of cyclobutane pyrimidine dimers

Chen-Hui Chan (1) , Francois Dehez (2) , Jean-Luc Ravanat (3) , Thierry Douki (3) , Antonio Monari (2) , Elise Dumont (1)

1 LC - Laboratoire de Chimie - UMR5182
2 LPCT - Laboratoire de Physique et Chimie Théoriques
3 CIBEST - Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie

Dimerization of two adjacent thymines and cytosines form cyclobutane pyrimidine dimers (CPD), produced upon UVB radiation in DNA. Thanks to nucleotide excision repair, these deleterious lesions are recognised and removed efficiently in order to prevent formation of skin cancer. It is known that the repair rate of CPD depend on the nucleobases involved in the lesion, and indeed experimental studies established that those containing tymine are repaired more slowly than those containing cytosine [1]. Here, we performed molecular dynamics simulations to rationalize the repair of DDB2 moiety with four different possible combination of CPD: T<>T, T<>C, C<>T, C<>C. Our simulation agree with experimental findings in term of repair rate, and our results highlighted the lost of recognition in the case of T<>T dimers where it is moving away from the hydrophobic binding pocket. [1] Mouret S., Charveron M., Favier A., Cadet J., and Douki T., 2008, DNA Repair (Amst), 7, 704-712

Mots clés: cyclobutane pyrimidine dimer; nucleotide excision repair; DDB2 enzyme; molecular dynamics

Domaines: Chimie; Modélisation et simulation

Chen-Hui Chan, Francois Dehez, Jean-Luc Ravanat, Thierry Douki, Antonio Monari, et al.. Theoretical insight into different repair rates of cyclobutane pyrimidine dimers. Fifteenth edition of the international Workshop on Radiation Damage to DNA, May 2018, Aussois, France. ⟨hal-02124572⟩