辐射,复制应激或染色体分离错误诱导的微核不会激活cGAS-STING
Tohru Takaki1, Rhona Millar2, Crispin T Hiley3
1DSB Repair Metabolism Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Molecular cell
|May 15, 2024
概括
由基因毒性压力形成的微核不会激活干扰素基因 (STING) 途径的循环氨酸单酸盐 (GMP) -AMP合成酶 (cGAS) -刺激器. 微核中的基因组结合DNA抑制了cGAS激活,尽管cGAS局部化.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 循环氨酸单酸 (GMP) -AMP合成酶 (cGAS) -刺激干扰素基因 (STING) 途径对于对病毒和自身免疫的先天免疫非常重要.
- 由基因毒性压力引起的微核被认为是激活这种途径的原因.
研究的目的:
- 通过各种基因毒性攻击诱导的微核对cGAS-STING通路的激活进行研究.
- 确定潜在的cGAS-STING通路激活或微核抑制背后的机制.
主要方法:
- 使用电离辐射,复制应激和染色体分离错误诱导微核.
- 分析cGAS局部化,cGAMP生产,以及下游的STING,TBK1和IRF3酸化.
- 评估IRF3核积累和干扰素刺激的基因表达.
- 测试细胞对dsDNA和修饰的疫苗病毒的反应作为对照.
主要成果:
- cGAS局部化到破裂的微核,但没有激活cGAS-STING通路.
- 没有观察到cGAMP的产生,STING/TBK1/IRF3的酸化或IRF3的核积累.
- 由基因毒性压力诱导的微核含有与基因素结合的自我DNA,这抑制了cGAS激活.
- 该cGAS-STING通路仍然对外部dSDNA和病毒感染有反应.
结论:
- 由基因毒性压力形成的微核不会通过cGAS-STING通路触发天生的免疫信号.
- 微核中的基因组结合DNA作为cGAS激活的抑制剂.
- 这一发现挑战了微核在基因毒性压力下激活cGAS-STING介导免疫力的拟议作用.
关键词:
造成的DNA损伤是DNA损伤.在 IRF3 中,IRF3 是 IRF3 的一个类型.刺痛是一种刺痛.cGAS 是一个气体.染色体错误分离的错误分离是什么天生的免疫反应.微核是微核中的一个.辐射辐射辐射辐射的辐射复制压力是复制的压力.更多相关视频
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