美国加州大学圣地亚哥分校Arshad Desai和Pablo Lara-Gonzalez研究组合作取得最新进展。他们发现在未粘附动粒上催化Mad2-Cdc20组装的三元机制。这一研究成果发表在2021年1月1日出版的国际学术期刊《科学》杂志上。

他们用探针特异性地阐明了线粒体催化的Mad2-Cdc20组装机制，该探针专门监测活细胞中动粒的组装反应。他们发现，催化作用是通过三元机制发生的，该机制包括Mad2和Cdc20底物的局部递送以及两个磷酸化依赖性相互作用，这些相互作用在几何上限制了它们的位置以及起始Cdc20与Mad2相互作用。这些结果揭示了未粘附的动粒如何产生确保细胞分裂过程中基因组完整性的信号。

据悉，在细胞分裂过程中，动粒将染色体与纺锤体微管结合。为了防止染色体获得或丢失，缺乏微管附着的动粒局部催化检查点蛋白Cdc20和Mad2的缔合，这是形成可扩散的检查点复合物以防止有丝分裂失败的关键事件。

附：英文原文

Title: A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores

Author: Pablo Lara-Gonzalez, Taekyung Kim, Karen Oegema, Kevin Corbett, Arshad Desai

Issue&Volume: 2021/01/01

Abstract: During cell division, kinetochores couple chromosomes to spindle microtubules. To protect against chromosome gain or loss, kinetochores lacking microtubule attachment locally catalyze association of the checkpoint proteins Cdc20 and Mad2, which is the key event in the formation of a diffusible checkpoint complex that prevents mitotic exit. We elucidated the mechanism of kinetochore-catalyzed Mad2-Cdc20 assembly with a probe that specifically monitors this assembly reaction at kinetochores in living cells. We found that catalysis occurs through a tripartite mechanism that includes localized delivery of Mad2 and Cdc20 substrates and two phosphorylation-dependent interactions that geometrically constrain their positions and prime Cdc20 for interaction with Mad2. These results reveal how unattached kinetochores create a signal that ensures genome integrity during cell division.

DOI: 10.1126/science.abc1424

Source: https://science.sciencemag.org/content/371/6524/64