在诱导DNA断裂期间将线粒体DNA转移到核基因组中
Jinchun Wu1, Yang Liu1, Liqiong Ou1
1State Key Laboratory of Protein and Plant Gene Research, Genome Editing Research Center, School of Life Sciences, PKU-THU Center for Life Sciences, Peking University, Beijing, China.
Nature communications
|November 2, 2024
概括
基因组编辑,包括线粒体DNA编辑,可以导致线粒体DNA段转移到核基因组. 这种转移被压力和断裂加剧,但TREX核酶提供了一个解决方案.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 细胞的发电站线粒体拥有自己的DNA (mtDNA),使他们成为基因编辑治疗遗传疾病的目标.
- 在基因编辑后,mtDNA的稳定性及其与核基因组的相互作用在很大程度上仍未被描述.
研究的目的:
- 研究核和线粒体基因组编辑对mtDNA稳定性的影响.
- 为了确定与针对线粒体的基因编辑技术相关的风险.
- 探索减轻意外mtDNA转移的潜在解决方案.
主要方法:
- 利用了各种细胞类型,包括人类细胞系,初级T细胞和小鼠胚胎.
- 应用了基因编辑工具,如mitoTALEN和DdCBE.
- 诱导的线粒体应激和mtDNA断裂.
- 在编辑过程中共同表达的TREX1或TREX2外核酶.
主要成果:
- 在核基因组和线粒体基因组编辑后,证明了mtDNA段的可辨别转移到核基因组.
- 药物诱导的线粒体应激和mtDNA断裂显著加剧了这种转移.
- 观察到线粒体编辑器 (mitoTALEN,DdCBE) 增强了mtDNA与核基因组的交叉通话.
- 证实共表达TREX1/TREX2核酶可以减轻DdCBE诱导的mtDNA转移.
结论:
- 基因组编辑带来mtDNA不稳定性和转移到核基因组的风险.
- 线粒体应激和DNA断裂增加了mtDNA融入核DNA的可能性.
- TREX1/TREX2外核酶代表了一种可行的策略,可以防止基编辑过程中不必要的mtDNA转移.
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