Liu Yuanyuan, Liu Bohan, Zhang Ruirui, Zhu Zixuan, Zhao Li, Jiang Ruijie, Wang Yinghao, Qi Feifei, Wang Ruoxi, Zhao Huijie, Zhou Jun, Gao Jinmin
Center for Cell Structure and Function, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Shandong Normal University, Jinan 250014, China.
Department of Genetics and Cell Biology, State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University, Tianjin 300071, China.
J Mol Cell Biol. 2025 May 2;16(10). doi: 10.1093/jmcb/mjae047.
Cohesin is a ring complex closed with structural maintenance of chromosome 1 (SMC-1), SMC-3, and a kleisin subunit, mediating sister chromatid cohesion in mitosis and meiosis. Kleisin N- and C-terminal domains interact with SMC-3 and SMC-1, forming two distinct cohesin gates. Whether these gates are specialized for mitosis and meiosis remains elusive. Here, we create Caenorhabditis elegans mutants that express chimeric proteins swapping N- and C-terminal domains between different kleisins to investigate how these gates are specialized for different cell division programs. Replacing the meiotic REC-8 N-terminus with that of a cell division-unrelated kleisin COH-1 or the mitotic kleisin sister chromatid cohesion protein 1 (SCC-1) disrupts inter-sister chromatid cohesion and causes severe meiotic defects. Swapping the REC-8 C-terminus with that of COH-1 or SCC-1 largely retains the meiotic functions of REC-8 but causes age-related chromosome abnormalities. A specialized C-terminus is also required for the functions of SCC-1. Furthermore, point mutations in the REC-8 C-terminus cause severe meiotic defects without impairing the SMC-1-kleisin interaction, suggesting an integrated SMC-1-kleisin gate. These findings suggest the requirements for specialized cohesin gates in different biological processes.
黏连蛋白是一种由染色体结构维持蛋白1(SMC-1)、SMC-3和一个kleisin亚基组成的环状复合物,在有丝分裂和减数分裂中介导姐妹染色单体黏连。Kleisin的N端和C端结构域分别与SMC-3和SMC-1相互作用,形成两个不同的黏连蛋白门控。这些门控是否专门用于有丝分裂和减数分裂仍不清楚。在这里,我们构建了秀丽隐杆线虫突变体,这些突变体表达嵌合蛋白,在不同的kleisin之间交换N端和C端结构域,以研究这些门控如何专门用于不同的细胞分裂程序。用与细胞分裂无关的kleisin COH-1或有丝分裂kleisin姐妹染色单体黏连蛋白1(SCC-1)的N端替换减数分裂的REC-8 N端,会破坏姐妹染色单体间的黏连,并导致严重的减数分裂缺陷。将REC-8的C端与COH-1或SCC-1的C端交换,在很大程度上保留了REC-8的减数分裂功能,但会导致与年龄相关的染色体异常。SCC-1的功能也需要一个特殊的C端。此外,REC-8 C端的点突变会导致严重的减数分裂缺陷,而不会损害SMC-1-kleisin相互作用,这表明存在一个整合的SMC-1-kleisin门控。这些发现表明,在不同的生物学过程中需要特殊的黏连蛋白门控。