Histone modification via rapid cleavage of C4'-oxidized abasic sites in nucleosome core particles. Academic Article

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

• Sczepanski, Jonathan

author list (cited authors)

• Zhou, C., Sczepanski, J. T., & Greenberg, M. M

citation count

• 43

complete list of authors

• Zhou, Chuanzheng||Sczepanski, Jonathan T||Greenberg, Marc M

publication date

• January 2013

publisher

• American Chemical Society (ACS)  Publisher

published in

• Journal of the American Chemical Society  Journal

keywords

• Binding Sites
• DNA
• Histones
• Models, Molecular
• Molecular Structure
• Nucleosomes
• Oxidation-Reduction

PubMed Central ID

• 23531104

Digital Object Identifier (DOI)

• 10.1021/ja400915w

start page

• 5274

end page

• 5277

volume

• 135

issue

• 14

URL

• http%3A%2F%2Fdx.doi.org%2F10.1021%2Fja400915w