Shugoshin Regulates Cohesin, Kinetochore-Microtubule Attachments, and Chromosomal Instability.

IF 1.7 4区生物学 Q4 CELL BIOLOGY Cytogenetic and Genome Research Pub Date : 2022-01-01 Epub Date: 2023-03-02 DOI:10.1159/000528141

Qiqi Sun, Feng Liu, Xiaolong Mo, Bo Yao, Guanghai Liu, Shanshan Chen, Yanping Ren

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Abstract

Correct regulation of cohesin at chromosome arms and centromeres and accurate kinetochore-microtubule connections are significant for proper chromosome segregation. At anaphase of meiosis I, cohesin at chromosome arms is cleaved by separase, leading to the separation of homologous chromosomes. However, at anaphase of meiosis II, cohesin at centromeres is cleaved by separase, leading to the separation of sister chromatids. Shugoshin-2 (SGO2) is a member of the shugoshin/MEI-S332 protein family in mammalian cells, a crucial protein that protects centromeric cohesin from cleavage by separase and corrects wrong kinetochore-microtubule connections before anaphase of meiosis I. Shugoshin-1 (SGO1) plays a similar role in mitosis. Moreover, shugoshin can inhibit the occurrence of chromosomal instability (CIN), and its abnormal expression in several tumors, such as triple-negative breast cancer, hepatocellular carcinoma, lung cancer, colon cancer, glioma, and acute myeloid leukemia, can be used as biomarker for disease progression and potential therapeutic targets for cancers. Thus, this review discusses the specific mechanisms of shugoshin which regulates cohesin, kinetochore-microtubule connections, and CIN.

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舒戈欣调控粘合素、动轴-微管连接和染色体不稳定性

正确调节染色体臂和中心粒上的凝聚素以及动核与微管之间的准确连接对染色体的正确分离至关重要。在减数分裂第一阶段，染色体臂上的凝聚素被分离酶裂解，导致同源染色体分离。然而，在减数分裂第二阶段，中心粒上的内聚素会被分离酶裂解，导致姐妹染色单体分离。Shugoshin-2（SGO2）是哺乳动物细胞中shugoshin/MEI-S332蛋白家族的成员，它是一种重要的蛋白，能保护中心粒的凝聚素不被分离酶裂解，并在减数分裂I的无丝分裂前纠正错误的动核-微管连接。此外，舒戈欣还能抑制染色体不稳定性（CIN）的发生，它在多种肿瘤（如三阴性乳腺癌、肝细胞癌、肺癌、结肠癌、胶质瘤和急性髓性白血病）中的异常表达可作为疾病进展的生物标志物和癌症的潜在治疗靶点。因此，本综述讨论了 shugoshin 调节凝聚素、动核-微管连接和 CIN 的具体机制。

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来源期刊

Cytogenetic and Genome Research 生物-细胞生物学

CiteScore

3.10

自引率

5.90%

发文量

审稿时长

1 months

期刊介绍： During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.