有丝分裂期染色体分离的不断出错会引起染色体不稳定性。染色体不稳定性是多数肿瘤的普遍特征，也是肿瘤发生和转移的重要分子基础。申请人前期研究发现，HP1（Heterochromatin Protein 1）是调控染色体准确分离的一个关键蛋白，然而，对应的分子机制还不甚清楚。我们的前期实验结果显示，HP1α和HP1γ的双敲除会导致ATRX着丝粒定位的丧失，并且有丝分裂期HP1与ATRX存在相互作用。ATRX是一种染色体重塑蛋白，与地中海贫血症、神经胶质瘤等疾病的发生密切相关，然而其在有丝分裂期着丝粒定位的功能和机制还不清楚。我们在本项目中将深入分析有丝分裂期HP1结合ATRX的分子基础，探究二者结合调控姐妹染色单体粘连、染色体分离等方面的重要功能和分子机制。本项目将揭示HP1调控染色体准确分离的新机制，并为有丝分裂相关疾病的基因治疗提供新的分子靶标。

Chromosomal Instability (CIN), a hallmark for many types of cancer, promotes the tumorigenesis and metastasis, which is caused by errors in the segregation of chromosomes during mitosis. We have recently demonstrated that HP1 (Heterochromatin Protein 1) is one of the key proteins that regulate the fidelity of chromosome segregation; nevertheless, the molecular mechanism of HP1 remains largely elusive. In our preliminary study, we have revealed that centromeric ATRX on mitotic chromosomes is significantly reduced in HP1 DKO cells. We have also found the interaction between HP1 and ATRX. ATRX is a chromatin remodeling protein, which is closely related to thalassemia, glioma and other diseases. However, the function of ATRX at mitotic centromeres remains largely unknown. In this project, we aim to reveal the molecular basis for the ATRX-HP1 interaction. We shall utilize cellular and molecular technologies to explore the important roles of the ATRX-HP1 interaction in the regulation of cohesion and normal chromosome alignment in mitosis. This project would provide novel mechanisms for the regulation of chromosomal instability, and significantly, it would offer new molecular targets for gene therapy of mitosis-associated diseases.