组蛋白上胺氧高聚物的光驱动安装及其在合成稳定和特定位点的 3'-DNA-Histone 交叉连接中的应用。

IF 4 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-11-15 DOI:10.1021/acs.bioconjchem.4c00453

Yangxue Liu, Ying Peng, Zhishuo Wang, Xiaoying Wei, Kun Yang

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引用次数: 0

摘要

组蛋白与各种含醛 DNA 修饰发生反应，形成可逆但持久的 DNA 组蛋白交联。由于组蛋白的可逆性以及缺乏合成稳定和结构确定的 DNA 组蛋白交联的方法，对其生化效应和修复机制的研究一直受到阻碍。在这里，我们提出了一种可见光驱动的策略，在组蛋白的特定位置上安装一个氨基氧基组氨酸。利用这种方法，我们合成了一种水解稳定、位点特异的 3'-DNA 组蛋白交联，这种交联来源于消旋 DNA 病变。这种加合物可以通过蛋白水解和核酸酶切除有效修复。这项工作提供了一种策略，可以很容易地扩展到合成来自其他含醛 DNA 修饰的 DNA 组蛋白交联。

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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.

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来源期刊

Bioconjugate Chemistry Bioconjugate 生物-化学综合

CiteScore

9.00

自引率

2.10%

发文量

236

审稿时长

1.4 months

期刊介绍： Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.