Centromere Assembly

着丝粒组装

• 批准号: 1949653
• 负责人: Katsumi Kitagawa
• 金额: $ 100万
• 依托单位: University of Texas Health Science Center San Antonio
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1949653&HistoricalAwards=false
• 关键词: Centromere; Assembly

The processes that ensure accurate chromosome segregation in mitosis and meiosis are critical for cellular viability and stability. The centromere is an essential chromosomal structure with multiple functional roles necessary for faithful segregation of replicated chromosomes to daughter cells. This project will provide new insights into molecular mechanisms that lead to formation and maintenance of centromeres. In addition, the project will provide research and training opportunities to postdoctoral, graduate, undergraduate and high school students in the San Antonio area, many of whom are under-represented minorities and underprivileged.The goal of the project is to determine the factors and steps responsible for centromere formation and maintenance. Ubiquitylation of CENP-A protein is essential for CENP-A centromere deposition and assembly; hence, the hypothesis is that identification of ubiquitin-dependent CENP-A interactors will provide crucial information about mechanisms that control centromere assembly and maintenance. The following specific aims test this hypothesis: (1) determine the role of RAD50 (and the MRN complex) in CENP-A deposition at the centromere and its stability in centromeric nucleosomes (preliminary data implicate these proteins in ubiquitylation-dependent interactions with CENP-A); and (2) determine the role of R-loops in CENP-A deposition at the centromere (preliminary data implicate RNA helicase A, which is involved in R-loop formation and resolution, in ubiquitylation-dependent interactions with CENP-A). The intellectual significance of this work lies in novel mechanistic information that is vital to understanding the fidelity of chromosome segregation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

确保有丝分裂和减数分裂中染色体精确分离的过程对于细胞活力和稳定性至关重要。着丝粒是一种重要的染色体结构，具有将复制的染色体忠实地分离到子细胞所必需的多种功能作用。该项目将提供新的见解，导致形成和维持着丝粒的分子机制。此外，该项目将为圣安东尼奥地区的博士后、研究生、本科生和高中生提供研究和培训机会，其中许多人是代表性不足的少数民族和贫困人口，该项目的目标是确定负责着丝粒形成和维持的因素和步骤。CENP-A蛋白的泛素化对于CENP-A着丝粒沉积和组装是必不可少的;因此，假设是鉴定泛素依赖性CENP-A相互作用物将提供关于控制着丝粒组装和维持的机制的关键信息。以下具体目的检验这一假设：（1）确定RAD 50的作用（和MRN复合物）在CENP-A沉积在着丝粒及其在着丝粒核小体中的稳定性（初步数据表明这些蛋白质与CENP-A的泛素化依赖性相互作用）;以及（2）确定R环在CENP-A沉积在着丝粒中的作用（初步数据表明RNA解旋酶A参与R环的形成和分解，与CENP-A的泛素化依赖性相互作用）。这项工作的智力意义在于新的机制信息，这是至关重要的理解染色体分离的保真度。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。