在3D人类基因组组织中,核酸切除修复了阿弗拉托克辛诱导的DNA损伤
Yiran Wu1, Muhammad Muzammal Adeel1, Dian Xia1
1Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA.
Nucleic acids research
|September 11, 2024
概括
亚弗拉托辛B1 (AFB1) 的DNA损伤修复受基因组组织的影响. 转录合修复是关键,在核中心附近和A区,TAD边界和循环中修复率更高.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 毒理学 毒理学 毒理学
背景情况:
- 非洲毒素B1 (AFB1) 是一种真菌毒素,也是肝癌的环境风险因素.
- 生物激活的AFB1形成了重的DNA附加物,如果不修复,会导致突变.
研究的目的:
- 以单核酸分辨率测量AFB1诱导的DNA添加物的全基因组核酸切除修复 (NER).
- 为了比较AFB1 NER与紫外线损伤修复.
- 分析3D基因组组织内的AFB1 adduct修复分布.
主要方法:
- 适应tXR-seq方法用于全基因组AFB1 adduct修复测量.
- 与传统的紫外线损伤XR-seq数据进行比较.
- 分析染色体区域,A/B区,TAD和染色体循环中的修复分布.
主要成果:
- 转录合修复显著促进AFB1 adduct去除.
- 在不同的3D基因组组织水平上,AFB1-dG修复是异质的.
- 在靠近核中心的地区和A区内观察到更高的NER水平.
- 在TAD边界和循环处检测到较高的修复活动.
结论:
- 转录合修复对于消除AFB1诱导的DNA损伤至关重要.
- 3D基因组组织影响了AFB1 DNA修复的效率.
- 研究结果阐明了AFB1突变发生过程中DNA修复,转录和基因组架构之间的相互作用.
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