biostudies-literatureCai YNational Institute of Environmental Health SciencesEuropean Commission Directorate-General for Research and InnovationNCRR NIH HHSNIEHS NIH HHSMinistero dell'Istruzione, dell'Università e della RicercaNational Cancer InstituteNCI NIH HHS4181-5https://www.ebi.ac.uk/biostudies/studies/S-EPMC4862310biostudies-literatureUnknown54(27)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.BiochemistryDifferences in the Access of Lesions to the Nucleotide Excision Repair Machinery in Nucleosomes.PMC4862310R01 ES 011589CA28038R01 CA168469R01 CA028038PRIN-2009K3RH7N_002R01 CA075449298555R01 ES011589C06 RR016572Chatgilialoglu CKropachev KShafirovich VGeacintov NECai YTerzidis MAMasi ABroyde SfalseDifferences in the Access of Lesions to the Nucleotide Excision Repair Machinery in Nucleosomes.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.2015-01-01T00:00:00Z2015 Jul2024-11-20T03:19:22.868Z2019-03-27T02:13:26ZS-EPMC48623102609101610.1021/acs.biochem.5b00564