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Updated: Jun 7, 2025
Site Specific Lysine Acetylation of Histones for Nucleosome Reconstitution using Genetic Code Expansion in Escherichia coli
Published on: December 26, 2020
Light-Driven Installation of Aminooxyhomolysine on Histones and Its Application for Synthesizing Stable and
Yangxue Liu1, Ying Peng1, Zhishuo Wang1
1Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
Abstract:
Histones react with various aldehyde-containing DNA modifications to form reversible but long-lived DNA-histone cross-links. The investigation of their biochemical effects and repair mechanisms has been impeded due to their reversibility and the lack of methods for synthesizing stable and structure-defined DNA-histone cross-links. Herein, we present a visible-light-driven strategy to install an aminooxyhomolysine on a histone at a defined position. Using this method, we synthesized a hydrolytically stable and site-specific 3'-DNA-histone cross-link derived from an abasic DNA lesion. Such an adduct can be efficiently repaired by proteolysis coupled with nuclease excision. This work provides a strategy that can be readily expanded to synthesize DNA-histone cross-links derived from other aldehyde-containing DNA modifications.
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