title: Histone modification via rapid cleavage of C4'-oxidized abasic sites in nucleosome core particles.
abstract: The C4'-oxidized abasic site is produced in DNA by a variety of oxidizing agents, including potent cytotoxic antitumor agents. Independent generation of this alkali-labile lesion at defined positions within nucleosome core particles reveals that the histone proteins increase strand scission between 130- and 550-fold. Strand scission proceeds via a Schiff base intermediate, but the DNA-protein cross-links are unstable. The oxidized abasic site is removed in its entirety from the DNA and transferred to the lysine-rich tail region of the proximal histone protein in the form of a lactam. The modification is distributed over several residues within the amino-terminal tail of the proximal histone. Transfer of DNA damage to histones could affect gene regulation.
authors.affiliation: Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
authors.forename: Chuanzheng
authors.initials: C
authors.lastname: Zhou
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Sczepanski
authors.forename: Marc M
authors.initials: MM
authors.lastname: Greenberg
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D006657:Histones / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009707:Nucleosomes / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D006657:Histones; D009707:Nucleosomes; D004247:DNA