通过DNA细胞因子脱氨酶APOBEC3B编辑R循环,调节雌激素受体增强剂的活性
Chi Zhang1,2,3, Yu-Jing Lu4, Bingjie Chen5
1Centre for Cancer Drug Discovery, Division of Cancer Therapeutics, the Institute of Cancer Research, London, United Kingdom.
Nature communications
|February 17, 2026
概括
雌激素受体 (ER) 激活在调节区域通过APOBEC3B (A3B) 促进DNA断裂. 这一过程依赖于R循环和基因切除修复,影响基因激活和基因组不稳定.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 雌激素受体 (ER) 激活与DNA双链断裂 (DSB),基因组不稳定性和瘤异质性有关.
- APOBEC3B (A3B) 是一种DNA除氨酶,作为ER联合激活剂,在ER调节的转录增强剂中诱导DSB.
研究的目的:
- 调查A3B针对DNA的机制及其在ER介导的基因组不稳定性中的作用.
- 阐明R循环和基切除修复 (BER) 在A3B诱导的DSB和转录调节中的参与.
主要方法:
- 基因切除修复 (BER) 缺乏的细胞模型中的全基因组测序.
- 链特异性DNA:RNA免疫沉降测序 (ssDRIP-seq).
- ssDNA相关的蛋白质免疫沉降测序 (SPI-seq).
主要成果:
- A3B优先针对以R循环依赖的方式转录活跃的调节区域.
- 在R循环中,A3B与单链DNA (ssDNA) 结合并去胺,这一过程由ER交换激活增强.
- 由BER介导的A3B诱导的 uracil 基的处理有助于R环相关的DSB,这对于ER调节的基因激活至关重要.
结论:
- A3B在R循环恒温和转录调节中发挥着重要作用.
- A3B,R循环,BER和ER激活之间的相互作用有助于ER驱动的基因组不稳定.
- 研究结果表明A3B是ER驱动癌症的潜在治疗点.
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