Molecular dynamics investigation of DNA tandem lesions repair
Résumé
DNA integrity is constantly threatened by radicals and sunlight, leading to chemical modifications of nucleobases. For two neighboring simple DNA defects, the repair turns out to be dramatically lowered [1]. However the field suffers from X-ray or NMR structure to interpret the repair rate measurements of such tandem lesions (10% of the total 8-oxoguanines). Relying on all-atom explicit-solvent molecular dynamics, we explore the structure of oligonucleotides and DNA-enzyme systems featuring two oxidized guanine sites. Our simulations recover sequence effects [2] and provide atomic-scale structural insights into the lack of non-covalent interactions that induce a low repair of 8-oxoguanine and abasic sites with Nfo[2], APE1[3] and Fpg.
Domaines
Chimie
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