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

ABSTRACT: 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.

SUBMITTER: Cai Y

PROVIDER: S-EPMC4862310 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

Cai Yuqin Y Kropachev Konstantin K Terzidis Michael A MA Masi Annalisa A Chatgilialoglu Chryssostomos C Shafirovich Vladimir V Geacintov Nicholas E NE Broyde Suse S

Biochemistry 20150630 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 add ...[more]

PMID: 26091016

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