Differences in the Access of Lesions to the Nucleotide
Excision Repair Machinery in Nucleosomes
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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 <i>R</i> and <i>S</i> 5′-8-cyclo-2′-dG and the (+)-<i>cis-anti</i>-B[<i>a</i>]P-dG lesions in a nucleosome. Our results show
that the (+)-<i>cis-anti</i>-B[<i>a</i>]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 (+)-<i>cis-anti</i>-B[<i>a</i>]P-dG lesion