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

细胞分裂是我们生存的基础。从单个细胞中，大约有37.2万亿个细胞组成了一个成年人。分裂需要以非常准确的方式发生，以产生健康和可行的子细胞。细胞分裂缺陷是从唐氏综合症到癌症的几种人类病理学的基础。了解细胞分裂是如何忠实地发生的，以及如何避免错误，将使我们有更好的诊断工具和干预机会来预防或治愈其中一些疾病。在细胞分裂过程中分离染色体的关键机制是着丝粒/动粒。这种结构由DNA和与DNA直接相连的蛋白质组成，并在着丝粒处形成特殊的DNA结构，这对染色体分离至关重要。我最近发现了其中的一些蛋白质，当它们被改变时，会损害分离的保真度。该项目旨在确定这些蛋白质是如何工作的，它们如何有助于维持健康的细胞几代人，以及当它们功能失调时的直接后果是什么。这项研究的结果不仅将进一步加深我们对染色体分离机制的认识，而且还为药物干预提供了新的可能靶点。

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.