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有丝分裂之外的染色体凝聚:机制与新工具

Chromosome condensation outside of mitosis: mechanisms and new tools.

作者信息

Gotoh Eisuke, Durante Marco

机构信息

Division of Genetic Resources, National Institute of Infectious Diseases, Tokyo, Japan.

出版信息

J Cell Physiol. 2006 Nov;209(2):297-304. doi: 10.1002/jcp.20720.

Abstract

A basic principle of cell physiology is that chromosomes condense during mitosis. However, condensation can be uncoupled from mitotic events under certain circumstances. This phenomenon is known as "premature chromosome condensation (PCC)." PCC provides insights in the mechanisms of chromosome condensation, thus helping clarifying the key molecular events leading to the mitosis. Besides, PCC has proved to be an useful tool for analyzing chromosomes in interphase. For example, using PCC we can visualize genetic damage shortly after the exposure to clastogenic agents. More than 30 years ago, the first report of PCC in interphase cells fused to mitotic cells using Sendai virus was described (virus-mediated PCC). The method paved the way to a great number of fundamental discoveries in cytogenetics, radiation biology, and related fields, but it has been hampered by technical difficulties. The novel drug-induced PCC method was introduced about 10 years ago. While fusion-induced PCC exploits the action of external maturation/mitosis promoting factor (MPF), migrating from the inducer mitotic cell to the interphase recipient, drug-induced PCC exploits protein phosphatase inhibitors, which can activate endogenous intracellular MPF. This method is much simpler than fusion-induced PCC, and has already proven useful in different fields.

摘要

细胞生理学的一个基本原则是染色体在有丝分裂期间会浓缩。然而,在某些情况下,浓缩可能与有丝分裂事件解偶联。这种现象被称为“早熟染色体浓缩(PCC)”。PCC为染色体浓缩机制提供了见解,从而有助于阐明导致有丝分裂的关键分子事件。此外,PCC已被证明是分析间期染色体的有用工具。例如,使用PCC我们可以在接触致染色体断裂剂后不久可视化遗传损伤。30多年前,首次报道了使用仙台病毒将间期细胞与有丝分裂细胞融合后的PCC(病毒介导的PCC)。该方法为细胞遗传学、辐射生物学及相关领域的大量基础发现铺平了道路,但一直受到技术难题的阻碍。大约10年前引入了新型药物诱导的PCC方法。融合诱导的PCC利用外部成熟/有丝分裂促进因子(MPF)的作用,该因子从诱导性有丝分裂细胞迁移到间期受体细胞,而药物诱导的PCC利用蛋白磷酸酶抑制剂,其可激活内源性细胞内MPF。该方法比融合诱导的PCC简单得多,并且已在不同领域证明是有用的。

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