Regulation of catalytic activity and processivity of human telomerase
Regulation of catalytic activity and processivity of human telomerase
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DOI：
10.1021/bi982249n
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发表时间：
1999-03-30
期刊：
影响因子：
2.9
通讯作者：
Von Hoff, DD
中科院分区：
文献类型：
--
作者：
Sun, D;Lopez-Guajardo, CC;Von Hoff, DD
真核生物染色体的末端是专门的序列，称为端粒，包含简单DNA序列的串联重复。这些序列对于防止异常重组和保护基因组DNA免受核酸外切降解是必需的。端粒通过端粒酶（一种RNA依赖的DNA聚合酶）维持在稳定的长度。近年来，端粒酶被认为是人类肿瘤的特异性诊断标志物，并有望成为抗肿瘤药物的高选择性靶点。在这项研究中，我们研究了影响端粒酶催化活性和持续合成能力的主要因素。具体而言，人端粒酶的催化活性和持续合成能力都受到温度、底物（dNTP和引物）浓度和K+浓度的调节。随着温度（高达37摄氏度）、dGTP、引物和K+浓度的增加，端粒酶的催化活性增加。然而，随着温度、引物浓度和K+的增加，人端粒酶的持续合成能力下降。我们的研究结果支持了目前的人类端粒酶反应模型，并加强了端粒DNA的G-四链体结构在端粒酶反应的调节中起着重要作用的假设。
The ends of eukaryotic chromosomes are specialized sequences, called telomeres comprising tandem repeats of simple DNA sequences. Those sequences are essential for preventing aberrant recombination and protecting genomic DNA against exonucleolytic DNA degradation. Telomeres are maintained at a stable length by telomerase, an RNA-dependent DNA polymerase. Recently, human telomerase has been recognized as a unique diagnostic marker for human tumors and is potentially a highly selective target for antitumor drugs. In this study, we have examined the major factors affecting the catalytic activity and processivity of human telomerase. Specifically, both the catalytic activity and processivity of human telomerase were modulated by temperature, substrate (dNTP and primer) concentration, and the concentration of K+. The catalytic activity of telomerase increased as temperature (up to 37 degrees C), concentrations of dGTP, primer, and K+ were increased. However, the processivity of human telomerase decreased as temperature, primer concentration, and K+ were increased. Our results support the current model for human telomerase reaction and strengthen the hypothesis that a G-quadruplex structure of telomere DNA plays an important role in the regulation of the telomerase reaction.