Light-Driven Installation of Aminooxyhomolysine on Histones and Its Application for Synthesizing Stable and Site-Specific 3′-DNA–Histone Cross-Links
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.
Authors
- Ying Peng (ORCID: https://orcid.org/0000-0003-4654-1737)
- Zhishuo Wang (ORCID: https://orcid.org/0009-0004-2201-3686)
- Kun Yang (ORCID: https://orcid.org/0000-0001-5532-8810)
- Y M Liu
- Xiaoying Wei (ORCID: https://orcid.org/0000-0002-5562-7439)
Institutions
- The University of Texas at Austin (US)
Publication Details
- Journal
- Bioconjugate Chemistry
- Published
- 2024-11-15
- DOI
- https://doi.org/10.1021/acs.bioconjchem.4c00453
- Citations
- 2
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- University of Texas at Austin
- National Institutes of Health
- National Institute of General Medical Sciences