Role of TZAP in telomere homoeostasis

TZAP 在端粒稳态中的作用

• 批准号: 9287273
• 负责人: Eros Lazzerini Denchi
• 金额: $ 38.7万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9287273
• 关键词: Address; Aplastic Anemia; BTB/POZ Domain; Binding; Binding Proteins; Biology; C-terminal; Cells; Chromatin; Chromosomes; Complex; DNA; Data; Dyskeratosis Congenita; Genome Stability; Germ Cells; Goals; Hamman-Rich syndrome; Homeostasis; Homodimerization; Human; Knockout Mice; Length; Malignant Neoplasms; Mediating; Modeling; Molecular; NBS1 gene; Nucleoproteins; Physiological; Play; Premature aging syndrome; Process; Property; Protein Overexpression; Proteins; Proteomics; Protocols documentation; Recruitment Activity; Regulation; Research; Research Proposals; Role; Stem cells; Structure; TERF1 gene; Telomerase; Telomere Shortening; Testing; Tissues; XRCC3 gene; Zinc Fingers; base; cancer cell; homologous recombination; human disease; in vivo; insight; mouse model; novel; overexpression; response; role model; telomere

Project Summary The goal of this proposal is to investigate the role of a novel Telomere associated protein that we termed TZAP in telomere homeostasis. Telomeres are essential nucleoprotein structures that cap chromosome ends. Alterations in telomere function are associated with various human diseases including cancer, premature aging, dyskeratosis congenita, aplastic anemia, and idiopathic pulmonary fibrosis. Our preliminary data show that TZAP is a novel telomere specific binding protein that is involved in telomere length homoeostasis. Several questions remain to be addressed to define the role of this novel telomere associated protein in telomere homeostasis. To address this questions, we have devised a research proposal that will define the mechanism of TZAP binding to telomeres, its role on telomere length regulation and the impact of its depletion in respect to genome stability and tissue homoeostasis.

项目摘要 这项计划的目的是研究一种新的端粒相关蛋白的作用， 我们称之为TZAP。端粒是核蛋白的基本结构 覆盖染色体末端。端粒功能的改变与各种人类 疾病，包括癌症、早衰、先天性角化不良、再生障碍性贫血和 特发性肺纤维化我们的初步数据表明，TZAP是一个新的端粒特异性 参与端粒长度稳态的结合蛋白。还有几个问题有待解决 目的是确定这种新的端粒相关蛋白在端粒稳态中的作用。 为了解决这个问题，我们设计了一个研究方案， TZAP与端粒的结合，其对端粒长度调节的作用以及其对端粒长度调节的影响。 在基因组稳定性和组织内稳态方面的消耗。