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

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• 作者：Yuqin Cai ; Konstantin Kropachev ; Michael A. Terzidis ; Annalisa Masi ; Chryssostomos Chatgilialoglu ; Vladimir Shafirovich ; Nicholas E. Geacintov ; Suse Broyde
• 刊名：Biochemistry
• 出版年：2015
• 出版时间：July 14, 2015
• 年：2015
• 卷：54
• 期：27
• 页码：4181-4185
• 全文大小：422K
• ISSN：1520-4995

文摘

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鈥?8-cyclo-2鈥?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鈥?8-cyclo-2鈥?dG lesions, suggesting more facile access to the more bulky (+)-cis-anti-B[a]P-dG lesion.