Molecular mechanisms for the final step of dissolving sister chromatid cohesion at anaphase onset

后期开始时溶解姐妹染色单体凝聚力最后一步的分子机制

• 批准号: BB/S007768/1
• 负责人: Tomoyuki Tanaka
• 金额: $ 54.94万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS007768%2F1
• 关键词: Molecular; mechanisms; final; step; dissolving

To make a human body from a single cell (a fertilized egg), an enormous number of cell divisions must take place. Each cell division produces two daughter cells, which equally inherit genetic information from their mother cell. Human cells store their genetic information within 46 structures called chromosomes. To maintain this genetic information, all chromosomes must be precisely copied and each daughter cell must receive one copy of each chromosome when cell division takes place. Failure in this process may cause cancers and genetic abnormalities. The aim of our research is to clarify the fundamental mechanisms by which all chromosomes are properly inherited by daughter cells.In this research project, we focus on the special glue between copied chromosomes. As mentioned above, all chromosomes must be copied and each copy must be given to newly born daughter cells. It is crucial that copied chromosomes are held together with the special glue. However, at right timing, the glue must be quickly removed so that each chromosome copy is given to each daughter cell. If the glue is lost too early, chromosomes are mixed up and not correctly given to daughter cells. On the other hand, if removal of the glue is delayed, chromosome copies do not separately at right time, and both copies could be given to one daughter cell (rather than each copy to each daughter). We will study how cells regulate removal of the glue between copied chromosomes and what mechanisms ensure efficient removal of the glue. We will use both yeast and human cells in our study since they have many similarities in regulation of the chromosome glue. Use of yeast often allows us to reach conclusion more quickly. We will then address if the glue is regulated in the same way in human cells.

要从一个细胞（受精卵）形成人体，必须进行大量的细胞分裂。每一次细胞分裂产生两个子细胞，子细胞从母细胞平等地继承遗传信息。人类细胞将其遗传信息存储在46个称为染色体的结构中。为了保持这种遗传信息，所有的染色体必须精确地复制，并且当细胞分裂发生时，每个子细胞必须接收每个染色体的一个拷贝。这个过程的失败可能会导致癌症和遗传异常。我们的研究目的是阐明子细胞正确继承所有染色体的基本机制。在本研究项目中，我们专注于复制染色体之间的特殊粘合剂。如上所述，所有的染色体都必须被复制，并且每个拷贝都必须被给予新出生的子细胞。复制的染色体用特殊的胶水粘在一起是至关重要的。然而，在正确的时间，胶水必须迅速去除，以便将每个染色体拷贝提供给每个子细胞。如果胶水过早丢失，染色体就会混淆，不能正确地传递给子细胞。另一方面，如果胶水的去除被延迟，染色体拷贝就不能在正确的时间分开，两个拷贝都可以被给予一个子细胞（而不是每个拷贝给每个子细胞）。我们将研究细胞如何调节复制染色体之间的胶水的去除，以及什么机制确保胶水的有效去除。我们将在我们的研究中使用酵母和人类细胞，因为它们在调节染色体胶方面有许多相似之处。使用酵母通常可以让我们更快地得出结论。然后，我们将讨论这种胶水在人类细胞中是否以同样的方式受到调节。

项目成果

Smc3 Deacetylation by Hos1 Facilitates Efficient Dissolution of Sister Chromatid Cohesion during Early Anaphase.

Hos1 对 Smc3 的去乙酰化促进早期后期姐妹染色单体凝聚力的有效溶解。

• DOI: 10.1016/j.molcel.2020.04.036
• 发表时间: 2020
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Li S