Histone Modification via Rapid Cleavage of C4 '-Oxidized Abasic Sites in Nucleosome Core Particles

作者：Zhou Chuanzheng; Sczepanski Jonathan T; Greenberg Marc M^*

来源：Journal of the American Chemical Society, 2013, 135(14): 5274-5277.

DOI：10.1021/ja400915w

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.

• 出版日期2013-4-10