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Differences in the Access of Lesions to the Nucleotide Excision Repair Machinery in Nucleosomes

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journal contribution
posted on 14.07.2015, 00:00 authored by Yuqin Cai, Konstantin Kropachev, Michael A. Terzidis, Annalisa Masi, Chryssostomos Chatgilialoglu, Vladimir Shafirovich, Nicholas E. Geacintov, Suse Broyde
In nucleosomes, the access of DNA lesions to nucleotide excision repair is hindered by histone proteins. However, evidence that the nature of the DNA lesions may play a role in facilitating access is emerging, but these phenomena are not well-understood. We have used molecular dynamics simulations to elucidate the structural, dynamic, and energetic properties of the R and S 5′-8-cyclo-2′-dG and the (+)-cis-anti-B­[a]­P-dG lesions in a nucleosome. Our results show that the (+)-cis-anti-B­[a]­P-dG adduct is more dynamic and more destabilizing than the smaller and more constrained 5′,8-cyclo-2′-dG lesions, suggesting more facile access to the more bulky (+)-cis-anti-B­[a]­P-dG lesion.

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