《生命科学》 2024, 36(11): 1428-1438

黏连蛋白及其调控因子对疾病发生的影响

张晶晶¹ , 佟　琳¹ , 曹可新¹ , 张　政¹ , 齐睿权¹ , 魏　杰¹ , 楼慧强² , 曹向宇^1,* , 龚　平^3,*

¹辽宁大学生命科学院，沈阳 110036 ²深圳大学医学部，深圳 518073 ³湖南省微生物研究院，长沙 410009

摘　要：

遗传物质的准确传递是基因组维持稳定性的重要前提。遗传物质的传递主要包括染色体的复制和分离。姐妹染色单体黏连(sister chromatid cohesion, SCC) 是保证复制生成的两条姐妹染色单体被均等地分配到两个子细胞的关键过程。SCC 过程中姐妹染色单体由黏连蛋白(cohesin, Smc1-Smc3-Scc1-Scc3) 捆绑在一起。黏连蛋白及调控因子的突变往往导致癌症及“黏连病”(cohesinopathies)。黏连病是一类导致智力和发育障碍的罕见病。最常见的有德朗热综合征(Cornelia de Lange syndrome, CdLS) 和罗伯茨综合征(Roberts syndrome, RBS)，这两类患者的症状类似，表现为面部畸形、发育迟缓，并伴随多发畸形或肿瘤等。本文将简要概述黏连病的驱动基因突变及其分子调控机制的研究进展，并在此基础上对黏连病的致病机理和临床研究进行展望。

通讯作者：曹向宇 , Email:caoxiangyu@lnu.edu.cn 龚　平 , Email:lvguang3542@sina.com

The effects of cohesin and their regulatory factors on disease development

ZHANG Jing-Jing¹ , TONG Lin¹ , CAO Ke-Xin¹ , ZHANG Zheng¹ , QI Rui-Quan¹ , WEI Jie¹ , LOU Hui-Qiang² , CAO Xiang-Yu^1,* , GONG Ping^3,*

¹School of Life Science, Liaoning University, Shenyang 110036, Chhina ²Medical School, Shenzhen University, Shenzhen 518073, China ³Hunan Institute of Microbiology, Changsha 410009, China

Abstract:

Accurate transmission of genetic information is an important prerequisite for maintaining genome stability. Faithful inheritance of the genetic information depends on chromosome replication and segregation. Sister chromatid cohesion (SCC) is a key process to ensure that the two sister chromatids generated by DNA replication are equally distributed to the daughter cells. There is accumulated evidence to support that mutations in the cohesin complex and regulatory factors involved in sister chromatid cohesion (SCC) establishment often lead to cancer and "cohesionopathies". The most common cohesinopathies include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS), both of which have similar symptoms such as facial deformities, developmental delay, and the possibility of multiple anomalies. This article provides an overview of the key loci of genes related to cohesionopathies and cancer, and summarizes the research progress on their possible molecular regulatory mechanisms. Finally, we speculate some main topics in this field to expedite both fundamental and clinic research.

Communication Author：CAO Xiang-Yu , Email:caoxiangyu@lnu.edu.cn GONG Ping , Email:lvguang3542@sina.com