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The role of the Smc5/6 complex in nuclear organization

Smc5/6复合物在核组织中的作用

基本信息

批准号：
RGPIN-2017-04830
负责人：
Cobb, Jennifer
金额：
$ 2.91万
依托单位：
University of Calgary
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2020
资助国家：
加拿大
起止时间：
2020-01-01 至 2021-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711228
关键词：
role Smc5 complex nuclear organization

项目摘要

Structural maintenance of chromosomes (SMC) proteins form ring-like structures that interact with the genome to organize and restrict its movement. In eukaryotes, there are six different SMC proteins forming the core of three distinct heterodimeric complexes including 1. Cohesin (Smc1/Smc3), 2. Condensin (Smc2/Smc4), and 3. The Smc5/6 complex (Smc5/Smc6). SMC protein complexes are central to the process of how DNA is systematically packaged. Cohesin regulates sister chromatid cohesion after replication and condensin drives chromosome packaging and condensation as cells go into mitosis. In contrast, most work on Smc5/6 has been primarily performed in the context of homologous recombination (HR) and DNA repair. Emerging work from our lab recently showed that Smc5/6 also has a function in chromatin association with the nuclear periphery and in maintaining higher-order chromatin structure at telomeres. Chromosomes are organized in the nucleus and locate to preferred positions. The nuclear envelope has a central role in this process and is critical for maintaining the architecture of the genome. The nuclear periphery is a region inhibitory to recombination. Cohesin and condensin are involved in the spatial organization of the nucleus, however a role for Smc5/6 in nuclear organization has not been addressed. This is surprising because Smc5/6 binds to repeats in the genome including telomeres and the rDNA that localize to the nuclear periphery. Characterization of Smc5/6 in tethering chromatin at the periphery will provide a clearer understanding of how the complex functions to down-regulate inappropriate homologous recombination. Our central hypothesis: Smc5/6 binds repetitive elements such as telomeres and the rDNA localizing them to the nuclear periphery through interactions with inner nuclear membrane (INM) proteins. Our objectives for the current proposal include: Objective 1: Determine whether Smc5/6 has a role in tethering telomeres at the periphery. We will determine whether Smc5/6 is important for telomere interactions and tethering to Mps3. Objective 2: Examine the role of Smc5/6 in tethering the rDNA at the periphery. We will determine whether the localization of Smc5/6 at the rDNA is important for tethering repetitive elements to Heh1 and Nur1.

染色体结构维持（SMC）蛋白形成环状结构，与基因组相互作用，组织和限制其运动。在真核生物中，有六种不同的SMC蛋白形成三种不同的异二聚体复合物的核心，包括1。2.内聚蛋白（Smc1/Smc3）；冷凝素（Smc2/Smc4），和3。Smc5/6复合物（Smc5/Smc6）。SMC蛋白复合物是DNA系统包装过程的核心。内聚蛋白调节姐妹染色单体在复制后的内聚，在细胞进入有丝分裂时，凝聚蛋白驱动染色体的包装和凝聚。相比之下，大多数关于Smc5/6的研究主要是在同源重组（HR）和DNA修复的背景下进行的。我们实验室最近的新研究表明，Smc5/6在染色质与核外周的关联以及维持端粒的高阶染色质结构中也具有功能。