Characterization of new telomeric proteins in C. elegans

秀丽隐杆线虫新端粒蛋白的表征

• 批准号: 491577942
• 负责人: Dr. Falk Butter
• 金额: --
• 依托单位: Institut für molekulare Virologie und Zellbiologie (IMVZ)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/491577942?language=en
• 关键词: Characterization; new; telomeric; proteins; C.

Telomeres are the ends of linear chromosomes and consist of repetitive double- and single-stranded DNA sequences. Telomeres are bound by dedicated protein complexes, such as shelterin in mammals, which protect telomeres from DNA damage and assist in the maintenance of telomere integrity across cell divisions. However, a comprehensive understanding of the proteins interacting with the C. elegans telomere sequence is lacking. We previously used a quantitative proteomics approach to screen for proteins binding to C. elegans telomeres, and identified TEBP-1 and TEBP-2, two paralogs that associate to telomeres in vitro and in vivo. TEBP-1 and TEBP-2 form a telomeric complex with the known single stranded telomere-binding proteins POT-1, POT-2, and MRT-1. These results define the first telomere binding complex of C. elegans, including TEBP-1 and TEBP-2, two double-stranded telomere binders, which mediate opposite telomere dynamics. In this project, we want to further characterize the organization and functionality of this C. elegans complex using biochemical and molecular biology techniques. The complex architecture will be studied by in vitro and supplemented with functional characterization in vivo using mutants. Additionally, we will characterize the additional candidates from the proteomic screen for their function at telomeres.

端粒是线性染色体的末端，由重复的双链和单链DNA序列组成。端粒被专门的蛋白质复合物结合，例如哺乳动物中的shelterin，其保护端粒免受DNA损伤并协助维持端粒在细胞分裂中的完整性。然而，全面了解与C. elegans端粒序列缺失。我们以前使用定量蛋白质组学方法来筛选与C. elegans端粒，并鉴定了TEBP-1和TEBP-2，这两种旁系同源物在体外和体内与端粒相关。TEBP-1和TEBP-2与已知的单链端粒结合蛋白POT-1、POT-2和MRT-1形成端粒复合物。这些结果确定了C. elegans，包括TEBP-1和TEBP-2，两个双链端粒结合剂，介导相反的端粒动力学。在这个项目中，我们希望进一步描述这个C的组织和功能。elegans复杂的生物化学和分子生物学技术。将通过体外研究复合物结构，并使用突变体补充体内功能表征。此外，我们将从蛋白质组学筛选中表征其在端粒中的功能的额外候选物。