Mechanisms of Sister Telomere Cohesion and Resolution

描述（由申请人提供）： 本研究的目的是阐明调节人类细胞中姐妹端粒凝聚力的机制。端粒是独特的异染色质结构，需要专门的机制来复制，保护和凝聚。S期姐妹端粒之间的凝聚力的建立对于细胞周期G2期的同源重组和DNA修复是必不可少的，并且在有丝分裂时姐妹端粒之间的凝聚力的及时解决对于基因组的完整性是至关重要的。我们在人类细胞中的研究表明，姐妹端粒需要不同的机制（与姐妹臂和着丝粒相比），在S期建立凝聚力和有丝分裂的决议。在这里，我们试图阐明潜在的机制。在目标1中，我们将确定如何在端粒中建立凝聚力以及为什么它很重要。在目标2中，我们将确定在有丝分裂时如何从端粒中去除凝聚力，以及如果不这样做会发生什么。在目标3中，我们将探索一个新的假设（基于我们新的初步数据），即有丝分裂时的持久凝聚力是处理端粒功能障碍的一般细胞机制。!

DESCRIPTION (provided by applicant): Project Summary The goal of this research proposal is to elucidate the mechanisms that regulate sister telomere cohesion in human cells. Telomeres are unique heterochromatic structures that require specialized mechanisms for their replication, protection, and cohesion. Establishment of cohesion between sister telomeres in S phase is essential for homologous recombination and DNA repair in G2 phase of the cell cycle and timely resolution of cohesion between sister telomeres at mitosis is critical for genome integrity. Our studies in human cells have shown that sister telomeres require distinct mechanisms (compared to sister arms and centromeres) for cohesion establishment in S phase and resolution in mitosis. Here we seek to elucidate the underlying mechanisms. In Aim 1 we will determine how cohesion is established at telomeres and why it is important. In Aim 2 we will determine how cohesion is removed from telomeres at mitosis and what happens if it is not. And in Aim 3 we will explore a novel hypothesis (based upon our new preliminary data) that persistent cohesion at mitosis is a general cellular mechanism for dealing with telomere dysfunction. !