Mechanisms of Sister Telomere Cohesion and Resolution

姐妹端粒凝聚和解析机制

• 批准号: 8870304
• 负责人: SUSAN SMITH
• 金额: $ 31.24万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8870304
• 关键词: Aging; Anaphase; Aneuploidy; Animal Model; Binding; Cell Cycle; Cells; Centromere; Chromosomal Stability; Chromosomes; Complex; DNA Repair; Data; Deletion Mutation; Disease; Dyskeratosis Congenita; Fibroblasts; Functional disorder; G2 Phase; Goals; Health; Heterochromatin; Human; Inherited; Lead; Malignant Neoplasms; Mediating; Mitosis; Pancytopenia; Play; Poly(ADP-ribose) Polymerases; Process; Proteins; Recombinant DNA; Recruitment Activity; Repetitive Sequence; Research Proposals; Resolution; Role; S Phase; Saccharomycetales; Sister; Sister Chromatid; Stress; Structure; Surveys; TINF2 gene; Tankyrase; Telomere Recombination; Therapeutic; Yeasts; arm; base; cell growth; cohesin; cohesion; follow-up; genome integrity; homologous recombination; human disease; man; mutant; neoplastic cell; novel; overexpression; rRNA Genes; recombinational repair; telomere

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.

描述（由申请人提供）： 项目摘要 本研究计划的目标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，需要专门的机制来进行复制、保护和内聚。 S 期姐妹端粒之间的内聚力的建立对于细胞周期 G2 期的同源重组和 DNA 修复至关重要，而有丝分裂时姐妹端粒之间的内聚力的及时解决对于基因组完整性至关重要。我们对人类细胞的研究表明，姐妹端粒需要不同的机制（与姐妹臂和着丝粒相比）来实现 S 期的内聚力建立和有丝分裂的分解。在这里，我们试图阐明潜在的机制。在目标 1 中，我们将确定端粒上的内聚力是如何建立的以及它为何如此重要。在目标 2 中，我们将确定有丝分裂时端粒的内聚力如何被消除，以及如果没有消除会发生什么情况。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），即有丝分裂时的持续内聚力是处理端粒功能障碍的一般细胞机制。