Effect of the Spiroiminodihydantoin Lesion on Nucleosome Stability and Positioning.

ABSTRACT: DNA is constantly under attack by oxidants, generating a variety of potentially mutagenic covalently modified species, including oxidized guanine base products. One such product is spiroiminodihydantoin (Sp), a chiral, propeller-shaped lesion that strongly destabilizes the DNA helix in its vicinity. Despite its unusual shape and thermodynamic effect on double-stranded DNA structure, DNA duplexes containing the Sp lesion form stable nucleosomes upon being incubated with histone octamers. Indeed, among six different combinations of lesion location and stereochemistry, only two duplexes display a diminished ability to form nucleosomes, and these only by ∼25%; the other four are statistically indistinguishable from the control. Nonetheless, kinetic factors also play a role: when the histone pr

SUBMITTER: Norabuena EM 

PROVIDER: S-EPMC6299323 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature