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

作者：Cai Yuqin; Kropachev Konstantin; Terzidis Michael A; Masi Annalisa; Chatgilialoglu Chryssostomos; Shafirovich Vladimir; Geacintov Nicholas E^*; Broyde Suse

来源：Biochemistry, 2015, 54(27): 4181-4185.

DOI：10.1021/acs.biochem.5b00564

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-cydo-2'-dG and the (+)-cis-anti-B[a]P-dG lesions in a nudeosome. 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.

• 出版日期2015-7-14