The role of the Smc5/6 complex in DNA repair

染色体结构维持（SMC）蛋白在染色体组织的许多方面发挥作用 和DNA代谢过程，包括修复。SMC蛋白高度保守，形成环状结构， 与DNA相互作用的结构，组织和限制其运动。强调其重要性， SMC蛋白在生命的三个门中是保守的，并且它们的进化出现早于 组蛋白SMC蛋白是DNA在复制后如何系统包装的过程的核心， 在有丝分裂中分离。在真核生物中，有六种不同的SMC蛋白，形成三种不同的SMC蛋白的核心。 异二聚体复合物包括1.粘附素（Smc 1/Smc 3），2.缩合酶（Smc 2/Smc 4），和3. SMC5/6 复合体（Smc 5/Smc 6）。 Smc 5/6与基因组结合的全局模式显示在折叠的复制叉、端粒、rDNA和着丝粒处的峰富集。此外，该复合物也被募集到DNA双链断裂，但其在损伤部位的功能仍然难以捉摸。在Smc 5/6复合物中有六个非Smc元素（Nse 1 -6）。最近，我们对Nse 5进行了表征，发现它在SUMO化反应中起作用。Nse 5有两个假定的SUMO相互作用基序（西姆斯），当突变时，导致与SUMO相互作用的丧失。 该提案的主要目标是了解DNA损伤过程中SMC蛋白的基本动力学。更具体地说，我们将使用遗传学，生物化学和显微镜方法相结合，以调查Smc 5/6和sumoylation在DNA损伤修复中的作用。这些研究将为SMC复合物的基因组维护功能和DNA从母细胞到子细胞的准确传输提供新的见解。

Structural maintenance of chromosomes (SMC) proteins function in many aspects of chromosome organization and DNA metabolism processes including repair. The SMC proteins are highly conserved and form ring-like structures that interact with DNA, organizing and restricting its movement. Emphasizing their significance, SMC proteins are conserved in the three phyla of life and their evolutionary emergence predates that of histones. SMC proteins are central to the process of how DNA is systematically packaged after replication and segregated in mitosis. 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. Smc5/6 complex (Smc5/ Smc6). The global pattern of Smc5/6 binding to the genome shows peak enrichment at collapsed replication forks, telomeres, rDNA, and centromeres. In addition, the complex is also recruited to DNA double strand breaks, however its function at sites of damage remains elusive. Within the Smc5/6 complex there are six Non-Smc-Elements (Nse1-6). Recently, we characterized Nse5 and find it has a role in sumoylation reactions. Nse5 has two putative SUMO interacting motifs (SIMs) that when mutated, result in a loss of interaction with SUMO. The broad objective of this proposal is to understand the fundamental dynamics of SMC proteins during DNA damage. More specifically we will use a combination of genetics, biochemical, and microscopy methods to investigate the role of Smc5/6 and sumoylation in the repair of DNA damage. These studies will provide novel insight into the function of the SMC complex for genomic maintenance and the accurate transmission of DNA from mother to daughter cells.