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。
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.
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.
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