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调节介质DNA双链断裂形成的REC114-MEI4-IHO1复合体的表征

Hamida Laroussi¹, Ariadna B Juarez-Martinez¹, Aline Le Roy¹

¹Université Grenoble Alpes, CNRS, CEA, IBS, Grenoble, France.

The EMBO journal

|July 11, 2023

概括

介质重组依赖于由REC114,MEI4和IHO1.1调节的DNA双链断裂 (DSB). 这项研究揭示了它们的复杂相互作用,表明REC114作为DSB形成和基因组完整性的监管中心.

科学领域:

分子生物学分子生物学
遗传学是一个遗传学.
细胞生物学细胞生物学

背景情况:

介质重组开始于DNA双链断裂 (DSB),这对遗传多样性和生育至关重要.
在小鼠中,TOPOVIL复合物 (SPO11/TOPOVIBL) 催化了DSB的形成.
REC114,MEI4和IHO1是TOPOVIL活动的关键调节者,但它们的机制尚不清楚.

研究的目的:

阐明REC114,MEI4和IHO1调节介质重组的分子机制.
描述这些环境因素的结构组合和相互作用.

主要方法:

阿尔法Fold2蛋白质结构预测.
蛋白质复合体的生物化学表征.
蛋白质与蛋白质相互作用的分析.

主要成果:

鼠标REC114形成同位素;与MEI4结合为2:1异位素,然后二元化.
通过卷轴-卷轴相互作用,IHO1形成稳定的四聚体.
IHO1直接结合REC114的PH域,与TOPOVIBL和ANKRD31在相同的结合表面上进行竞争.
证据支持一个三元的IHO1-REC114-MEI4复合体.

结论:

REC114作为一个监管平台,调解与多个合作伙伴的互动.
这些发现提供了对介质性DSB形成调节的机制性见解.
了解这些相互作用对于在半变化过程中保持基因组完整性至关重要.

关键词:

DNA 双链断裂发生介质变化 (meiosis) 是一种变质的过程.蛋白质复合体蛋白质复合体蛋白质的结构是蛋白质的结构.再组合的复合方式.

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