IDENTIFICATION OF THE MOLECULAR PATHWAYS LINKING H2A.Z (H2AZ.1 and H2AZ.2) TO CHROMOSOME SEGREGATION FIDELITY

连接 H2A.Z（H2AZ.1 和 H2AZ.2）与染色体分离保真度的分子途径的鉴定

• 批准号: BB/V013920/1
• 负责人: Paola Vagnarelli
• 金额: $ 54.41万
• 依托单位: Brunel University London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV013920%2F1
• 关键词: IDENTIFICATION; MOLECULAR; PATHWAYS; LINKING; H2A.Z

Cell division is a fundamental process that is at the basis of our existence. From the single cell, about 37.2 trillion cells are generated to make up an adult human being. Divisions need to occur in an extremely accurate manner in order to produce daughter cells that are healthy and viable. Defects in cell division are at the basis of several human pathologies ranging from Down syndrome to cancer. Understanding how cell division occurs faithfully and how mistakes are avoided would lead us to better diagnostic tools and intervention opportunity to either prevent or cure some of these diseases. The key machinery for segregating the chromosomes during cell division is the centromere/kinetochore. This structure is composed of DNA and proteins that are directly linked to DNA and forms a special DNA structure at the centromere, which is essential for chromosome segregation. I recently identified some of these proteins that, when altered, compromise the fidelity of segregation. The project aims at identifying how these proteins work, how they contribute to maintain healthy cells for generations and what are the direct consequences when they mal-function. The outcome of this study would not only further our knowledge on the chromosome segregation machinery but also provide new possible targets for pharmacological interventions.

细胞分裂是我们存在的基本过程。从单个细胞中，产生了约37.2万亿个细胞以组成成年人。为了产生健康且可行的子细胞，需要以极为准确的方式进行分裂。细胞分裂的缺陷是基于几种从唐氏综合症到癌症的人类病理。了解细胞分裂的忠实发生以及如何避免错误将使我们获得更好的诊断工具和干预机会，以预防或治愈其中一些疾病。细胞分裂过程中隔离染色体的关键机制是Centromere/Kinetochore。该结构由DNA和蛋白质组成，与DNA直接相关并在Centromere形成特殊的DNA结构，这对于染色体分离至关重要。我最近确定了其中一些蛋白质，这些蛋白质会损害隔离的保真度。该项目旨在确定这些蛋白质的工作原理，它们如何为世代相传维持健康细胞做出贡献，以及当它们发生故障时的直接后果。这项研究的结果不仅会进一步我们对染色体隔离机制的了解，而且还为药理学干预提供了新的可能目标。