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Reactivity of the Major Product of C5'-Oxidative DNA Damage in Nucleosome Core Particles.


ABSTRACT: The major pathway for DNA damage following hydrogen atom abstraction from the C5'-position results in direct strand scission and concomitant formation of a 5'-aldehyde-containing nucleotide (e.g., T-al). We determined that the half-life of alkali-labile T-al in free DNA under physiological conditions varies from 5-12 days. T-al reactivity was examined at three positions within nucleosome core particles (NCPs). β-Elimination increased >2.5-fold when T-al was proximal to the lysine-rich histone H4 tail. No difference in reactivity between free DNA and NCPs was observed when T-al was distal from the histone tails. The position-dependent involvement of histone tails in T-al elimination was gleaned from experiments with sodium cyanoborohydride and histone protein variants. The enhancement of T-

SUBMITTER: Rana A 

PROVIDER: S-EPMC6397081 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature