通过限制PrimPol活动,核活性聚合迅速调解复制叉在应力时的重塑,从而限制PrimPol活动
Maria Dilia Palumbieri1, Chiara Merigliano2, Daniel González-Acosta1
1Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Nature communications
|November 28, 2023
概括
核活性纤维迅速响应DNA复制压力,通过减缓叉子进展和诱导叉子逆转. 损害核活性聚合物破坏了这一过程,突出了它在维持基因组稳定性方面的作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞拥有管理DNA复制压力的机制,涉及叉减速和逆转.
- 核组织,特别是核活性在复制叉的可塑性中的作用仍然不清楚.
研究的目的:
- 为了研究核活性在调节在基因毒性压力期间的复制叉动力学中的作用.
- 阐明核乙烯影响DNA复制和基因组稳定性的分子机制.
主要方法:
- 在活细胞和固定细胞中利用核活性探针可视化活性动力学.
- 采用化学和遗传方法来损害核激素聚合.
- 评估了复制分叉进展,分叉逆转以及PrimPol,RAD51和SMARCAL1.1等关键蛋白质的加载.
主要成果:
- 在基因毒性处理后,核活性丝的数量和长度迅速增加,与复制工厂联系.
- 抑制核活性蛋白聚合,可以防止叉子减速和逆转.
- 缺陷的活性蛋白聚合会导致放松Primpol负载,不受约束的DNA合成,并减少RAD51/SMARCAL1的招募.
- 损坏的核活性聚合会导致染色体不稳定性以PrimPol-依赖的方式.
结论:
- 核F-actin通过限制PrimPol活动来协调复制叉的可塑性.
- 核活性是细胞对基因毒性压力的反应和保持基因组完整性的关键决定因素.
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