ASH1L保护cis调节元件免受循环butan胺二元体诱导的影响
Michelle N Yancoskie1, Reihaneh Khaleghi1, Anirvinya Gururajan2
1Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich 8057, Switzerland.
Nucleic acids research
|June 17, 2024
概括
组织素甲基转移酶ASH1L保护增强DNA免受紫外线损伤,通过减少循环butan胺二元体的形成. 失去ASH1L会增加皮肤癌的DNA突变.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 已知基因组甲基转移酶ASH1L有助于DNA修复,特别是消除紫外线诱导的循环butan胺二聚体 (CPD).
- 与其他基因组区域相比,CPD切除在像增强剂这样的调节元素上更有效.
研究的目的:
- 调查ASH1L如何影响增强细胞稳定性和DNA损伤.
- 了解ASH1L在保护CPD诱导增强剂中的作用.
主要方法:
- 分析ASH1L-熟练和ASH1L-缺乏细胞中的DNA损伤地图.
- 模拟分子动力学以研究ASH1L的DNA结合相互作用.
- 在不同的DNA序列和基因组元素中比较CPD形成.
主要成果:
- ASH1L保护增强器序列免受紫外线诱导的CPD形成,除了促进修复外.
- ASH1L 特别减少了 C-含有二核酸的 CPD,而不是 TT 部位,并且不会影响其他 DNA 损伤.
- ASH1L的保护作用与H3K4me3和H3K27ac标记有关,并且涉及一个AT,不利于CPD形成.
结论:
- ASH1L充当调控元件的守护者,防止CPD形成和相关突变.
- 失去ASH1L功能导致增强剂的C->T转换增加,特别是在具有ASH1L突变的皮肤癌中.
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