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INTERACTIONS BETWEEN TELOMERIC DNA PRIMERS & TELOMERASE

端粒 DNA 引物之间的相互作用

基本信息

批准号：
2391794
负责人：
HE WANG
金额：
$ 2.99万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-03-02 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/2391794
关键词：
DNA directed DNA polymerase DNA primers intermolecular interaction telomerase telomere

项目摘要

The integrity of telomeres is essential for chromosomal stability and, it has been found recently, other cellular functions including nuclear division. The replenishment of telomeric sequences, lost gradually as a result of conventional DNA replication, is carried out by the specialized ribonucleoprotein reverse transcriptase/telomerase, which adds telomeric DNA to a DNA 3' end by copying an internal RNA template. Recent data including kinetic studies show that the interaction of telomerase with primer sequences 5' to the 3' region involved in base pairing to the RNA template is functionally important in primer recognition and translocation during processive elongation. This interaction has been proposed to be carried out by a second (lagging product) binding site of telomerase in the current 'two-site' models. This proposal will dissect this interaction at the molecular level. The specific aims are to 1) probe the specific contacts between the telomerase lagging product site and its DNA primer substrate by DNA footprinting analysis; 2) analyze the contribution of sequence-specific functional groups on DNA to the interaction of DNA primer with the lagging site of telomerase by functional modification interference assays; 3) study the role of the telomerase DNA in the interaction between telomerase and telomeric DNA primer. This study will provide insights into telomere biosynthesis and polymerization of nucleic acids in general.

端粒的完整性对于染色体的稳定性是必不可少的，最近发现，包括核在内的其他细胞功能组织。端粒序列的补充，作为一种常规DNA复制的结果，由专门的核糖核蛋白逆转录酶/端粒酶，增加端粒通过复制内部RNA模板将DNA复制到DNA 3‘端。最新数据包括动力学研究表明，端粒酶与与RNA碱基配对有关的5‘至3’区的引物序列模板在引物识别和识别中具有重要功能在过程伸长过程中的易位。这种互动一直是建议由第二个(滞后产物)结合位点进行端粒酶在目前的‘两位点’模型中。这项提案将仔细分析这种分子水平上的相互作用。具体目标为1) 探索端粒酶滞后产物位点之间的具体联系 DNA足迹分析；2)通过DNA足迹分析 DNA上的序列特异性官能团对DNA的贡献 DNA引物与端粒酶滞后位点的相互作用功能修饰干扰试验；3)研究端粒酶与端粒DNA相互作用中的端粒酶底漆。这项研究将为端粒的生物合成和一般的核酸聚合。