酵母EndoG通过降解细胞质DNA来防止基因组不稳定
Yang Yu1, Xin Wang2,3, Jordan Fox1
1Baylor College of Medicine, Department of Molecular and Human Genetics, One Baylor Plaza, Houston, TX 77030, USA.
Research square
|January 23, 2024
概括
酵母Nuc1核酶通过降解细胞质DNA,如线粒体DNA (mtDNA) 和逆转移体cDNA,防止核基因组的不稳定. 这种酶限制了有害的DNA插入,保持了基因组的稳定性.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 线粒体DNA (mtDNA) 和逆转移体cDNA在细胞质中释放,可以触发甲基动物的无菌炎症和疾病.
- 细胞质核酶降解这些DNA物种以减轻炎症,但它们在防止核基因组不稳定性方面的作用尚不清楚.
研究的目的:
- 确定负责调节细胞质DNA物种向核转移的特定核酶.
- 研究这种核酶在维持核基因组稳定性中的作用.
主要方法:
- 在酵母中利用基于安普利康序列的方法来分析数百万个DNA双链断裂 (DSB) 修复产品.
- 研究了Nuc1核酶对细胞质DNA (包括mtDNA和逆转移子cDNA) 插入和转移到核中的影响.
主要成果:
- 核mtDNA (NUMT) 和逆转移子cDNA插入在不分裂的静止阶段酵母细胞中显著增加.
- 酵母EndoG (Nuc1) 核酶限制了逆转移子cDNA插入和非常长mtDNA (>10 kb) 的转移,同时促进了短NUMT (~45-200 bp) 的形成.
- Nuc1还调节了酵母老化和半球变化期间细胞质DNA转移到细胞核.
结论:
- 通过降解潜在有害的逆转移子cDNA和长 mtDNA片段,Nuc1 保持了基因组的稳定性.
- 短NUMT可能来自不完全降解的mtDNA,这表明核酶活性和NUMT形成之间存在联系.
- 消除细胞质DNA的核酶在维持整体基因组稳定性方面发挥着至关重要的作用.
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