在飞行和复制后的DNA病变绕道之间,PRIMPOL确保了稳健的交换
Christopher Mellor1, Joelle Nassar1, Saša Šviković1
1Division of Protein & Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Nucleic acids research
|November 16, 2023
概括
当DNA损伤耐受性途径受到损害时,PRIMPOL重新启动DNA合成,对细胞存活至关重要. 它通过限制后复制性间隙长度来提高病变绕道和填空机制的有效性.
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:
- DNA复制需要损伤耐受性路径来克服模板障碍.
- 普林波尔重启DNA合成,但其与其他损伤耐受性通路的整合尚未完全理解.
- 关键途径包括REV1依赖的病变绕道和PCNA无处不在依赖的缺口填充.
研究的目的:
- 研究PRIMPOL与DNA损伤耐受路径的遗传相互作用.
- 阐明PRIMPOL在REV1和PCNA K164依赖通路中断后细胞存活中的作用.
主要方法:
- 在人类细胞系中进行全基因组的CRISPR/Cas9选.
- 在受损DNA损伤耐受性的条件下分析细胞存活率.
主要成果:
- 在依赖于病变的方式失去Y家族聚合酶REV1和POLη时,PRIMPOL对于细胞存活至关重要.
- 在很大程度上,PRIMPOL支持缺乏PCNA K164依赖性缺口填充的细胞的生存.
- 普林波最大限度地提高了REV1和PCNA K164R绕道之间的相互作用.
结论:
- 普林波尔是DNA损伤耐受性的关键组成部分,增强了病变绕道和缺口填充之间的相互作用.
- 依赖PRIMPOL的抑制限制了复制后间隙的长度,从而优化了DNA修复和细胞存活.
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