在S阶段进入时的转录抑制保护了多能细胞中的基因组完整性
Deniz Gökbuget1,2,3, Kayla Lenshoek1,2,3, Ryan M Boileau1,2,3
1The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
Nature structural & molecular biology
|September 11, 2023
概括
干细胞蛋白质FOXD3通过在S阶段暂时暂停基因转录来防止DNA复制压力. 这在快速分裂的细胞中保持了基因组的稳定性.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 巧合的转录和DNA复制可以导致复制压力和基因组不稳定.
- 快速分裂的小鼠多能干细胞是转录活跃的,经历高复制压力,但保持基因组完整性.
研究的目的:
- 研究多能干细胞中的转录抑制剂FOXD3在减轻复制应激和保持基因组完整性方面的作用.
主要方法:
- 研究了FOXD3缺失对小鼠多能干细胞复制应激和基因组完整性的影响.
- 在S阶段分析了在高转录基因附近的FOXD3结合.
- 研究了抑制RNA聚合酶II和基因素乙化的影响.
主要成果:
- 在S相进入时,FOXD3的转录抑制对于最小化复制应激至关重要.
- 急性Foxd3缺失导致了即时的复制压力,细胞循环停止,基因组不稳定性和亡.
- 丢失FOXD3增加了高度转录的基因的表达,同时抑制RNA聚合酶II或基因素乙化减少了复制压力.
结论:
- 在保持基因组完整性方面,FOXD3通过在S阶段暂时抑制转录起着中心作用.
- 这种机制使得多能干细胞在高复制压力下能够忠实地进行DNA复制.
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