Telomere Extension By Telomerase

Humans, like most eukaryotic organisms, add direct repeats to the telomere using a specialized DNA polymerase called telomerase. Telomerase is a ribonucleoprotein (RNP) complex minimally composed of a conserved protein subunit containing a reverse transcriptase domain (human telomerase reverse transcriptase, hTERT) and a template-containing RNA (human telomerase RNA component, hTERC, or hTR, hTER). The primer for telomerase is the G-rich single-strand overhang at the chromosome end. <br><br>Telomerase can perform multiple rounds of repeat synthesis. The reaction cycle has been inferred from in vitro studies of telomerase from multiple organisms and can be described as having four events: 1) DNA primer recognition, 2) RNA template alignment, 3) elongation, and 4) translocation. Telomeric DNA is recognized in part by a presumed "anchor site" in hTERT, which preferentially binds G-rich DNA, and this interaction can affect elongation and translocation steps. This interaction occurs 5' of the alignment of the RNA template with the end nucleotides of the chromosome. RNA alignment positions the template adjacent to the chromosome terminus. During elongation, the template directs sequential addition of nucleotides to the telomere end. After synthesis of a repeat is completed, relative movement of telomerase and the primer, termed translocation, repositions telomerase at the end of the newly added sequence to allow initiation of another round of repeat addition.

人类，如同大多数真核生物，通过一种称为端粒酶的专用DNA聚合酶将直接重复序列添加至端粒。端粒酶是一种由保守蛋白亚基组成的最小核糖核蛋白（RNP）复合物，该亚基包含一个反转录酶结构域（人类端粒酶反转录酶，hTERT）以及一个包含模板的RNA（人类端粒酶RNA成分，hTERC，或hTR，hTER）。端粒酶的引物是位于染色体末端的富含G的单链突出部分。端粒酶能够进行多轮重复序列的合成。通过多种生物体端粒酶的体外研究，反应周期已被推断，并可描述为包括四个事件：1）DNA引物识别，2）RNA模板对齐，3）延伸，和4）转移。端粒DNA部分通过hTERT中的一个假定的“锚定点”被识别，该位点优先结合富含G的DNA，这种相互作用可能影响延伸和转移步骤。此相互作用发生在RNA模板与染色体末端核苷酸对齐的5'端。RNA对齐将模板置于染色体末端附近。在延伸过程中，模板指导连续核苷酸被添加至端粒末端。重复序列合成完成后，端粒酶与引物的相对移动，称为转移，将端粒酶重新定位至新添加序列的末端，以便启动另一轮重复序列的添加。