Association of nucleoside diphosphate kinase nm23-H2 with human telomeres.
Association of nucleoside diphosphate kinase nm23-H2 with human telomeres.
复制标题
核苷二磷酸激酶 nm23-H2 与人类端粒的关联。
DOI：
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
H. Nishino
中科院分区：
文献类型：
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作者：
K. Nosaka;M. Kawahara;M. Masuda;Y. Satomi;H. Nishino
端粒是真核染色体的末端，是由特定蛋白质-DNA 复合物形成的重要结构，可保护染色体免遭降解和端到端融合。 TRF1 是一种双链端粒 TTAGGG 重复结合蛋白，与哺乳动物端粒相关，并通过抑制端粒酶的作用来控制端粒长度。我们通过酵母双杂交筛选将人核苷二磷酸激酶 nm23-H2 鉴定为人 TRF1 相互作用蛋白。使用不同重组核苷二磷酸激酶的体外结合测定表明，TRF1 主要结合 nm23-H2 同工型，而不是 nm23-H1。电泳迁移率变动分析表明，重组nm23-H2蛋白可以结合单链端粒TTAGGG重复序列，但不能结合双链端粒重复序列。合成的20碱基寡核糖核苷酸由模板序列CUAACCCUAAC和人端粒酶RNA成分的相邻区域组成，也被发现与重组nm23-H2蛋白形成复合物。此外，在体外，大量 nm23-H2 蛋白的存在增加了端粒酶与其底物的亲和力。这些发现表明 nm23-H2 与人类端粒之间存在密切关系，并表明核苷二磷酸激酶具有新的生物学作用。
Telomeres, the ends of eukaryotic chromosomes, are essential structures formed by specific protein-DNA complexes that protect chromosomes from degradation and end-to-end fusion. TRF1, a double-stranded telomeric TTAGGG-repeat binding protein, is associated with mammalian telomeres and controls telomere length by inhibiting the action of telomerase. We identified human nucleoside diphosphate kinase nm23-H2 as a human TRF1-interacting protein by yeast two-hybrid screening. In vitro-binding assays using different recombinant nucleoside diphosphate kinases showed that TRF1 predominantly binds the nm23-H2 isoform rather than nm23-H1. Electrophoretic mobility shift analysis revealed that the recombinant nm23-H2 protein can bind the single-stranded telomeric TTAGGG-repeat while it cannot bind the double-stranded telomeric repeat. The synthetic 20 base oligoribonucleotide, which consists of the template sequence CUAACCCUAAC and the adjacent region of the RNA component of human telomerase, was also found to form the complex with the recombinant nm23-H2 protein. Furthermore, the affinity of telomerase for its substrate was increased in vitro by presence of the plentiful nm23-H2 protein. These findings indicate a close relationship between nm23-H2 and human telomeres and suggest a new biological role for nucleoside diphosphate kinase.
影响因子：
11.1
作者：
V. Zakian
通讯作者：
V. Zakian