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介质激酶模块调节了DNA损伤后的细胞周期重新进入和转录反应

Gönen Memişoğlu^1,2,3, Stefan Bohn⁴, Nevan J Krogan^4,5,6

¹Department of Molecular Genetics and Cell Biology, The University of Chicago, IL, 60637, USA.

bioRxiv : the preprint server for biology

|June 6, 2025

概括

介质Cdk8激酶模块 (CKM) 通过减弱转录来调节DNA损伤反应 (DDR). 这一基本的功能,在物种中得到保护,有助于DNA修复和细胞循环重新进入.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
遗传学遗传学是一个

背景情况:

调解者复合体通过RNA聚合酶II (RNAPII) 调节转录.
Cdk8激酶模块 (CKM) 是Mediator的一个可分离的子复合体.
在此之前,CKM在DNA损伤反应 (DDR) 中的作用是未知的.

研究的目的:

为了研究调解者CKM在DNA损伤反应中的功能.
阐明CKM影响DNA损伤转录的机制.
为了确定CKM在DDR中的作用是否在物种之间得到保护.

主要方法:

在酵母中进行基因查,以确定参与DDR的基因.
生物化学测定用于研究RNAPII与Mediator的结合.
显微镜分析在DNA断裂时的CKM定位.
在酵母和哺乳动物细胞中对CKM功能进行比较分析.

主要成果:

一个单一的DNA断裂触发了CKM依赖的全球转录衰减.
CKM激酶活性对抗RNAPII与Mediator的结合,从而降低转录.
CKM局部化到DNA断裂,抑制RNAPII结合.
这种CKM的DDR作用是从酵母保存到哺乳动物.

结论:

调解者CKM在DNA损伤反应中起着关键的,保存的作用.
通过CKM介导的转录衰减对于DDR无活化和基因组稳定性至关重要.
在DNA修复过程中,CKM作为转录的多方面的调节者.

关键词:

在Cdk8激酶模块中对DNA损伤的反应反应转录的媒介转录的媒介在 RNAPIIII 中.

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