Multiple Mechanisms Contribute To Telomere Maintenance.
Multiple Mechanisms Contribute To Telomere Maintenance.
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发表时间：
2013-11
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通讯作者：
T. Morrish;Dulat Bekbolysnov;David C Velliquette;Michelle Morgan;Bryan Ross;Yongheng Wang;Benjamin Chaney;Jessica L. McQuigg;Nathan Fager;I. Maine
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作者：
T. Morrish;Dulat Bekbolysnov;David C Velliquette;Michelle Morgan;Bryan Ross;Yongheng Wang;Benjamin Chaney;Jessica L. McQuigg;Nathan Fager;I. Maine
肿瘤的无限生长潜力取决于端粒维持，并且通常取决于端粒酶，一种RNA依赖性DNA聚合酶，其逆转录端粒酶RNA模板，在染色体末端合成端粒重复序列。在各种模式生物中进行的端粒酶基因缺失的研究表明，几种基于重组的机制也有助于端粒的维持。了解这些机制的分子基础是至关重要的，因为一些人类肿瘤的形成没有端粒酶，但序列保持在端粒。在表达端粒酶的肿瘤中，基于端粒酶的机制也可能以一定的频率有助于端粒的维持。防止端粒维持预计会影响肿瘤生长，但抑制端粒酶可能会选择基于重组的机制。端粒重组机制可能涉及改变或不受调控的DNA修复途径。一些DNA损伤剂的使用可以鼓励使用这些未调节的DNA修复途径，并且可以允许一些肿瘤产生对这些药物的抗性，这取决于肿瘤中哪些修复途径被改变。这篇综述将讨论各种端粒重组机制，并将提供有关的可能性，L1逆转录酶可能有助于端粒维持缺乏端粒酶的肿瘤的理由。
The unlimited growth potential of tumors depends on telomere maintenance and typically depends on telomerase, an RNA-dependent DNA polymerase, which reverse transcribes the telomerase RNA template, synthesizing telomere repeats at the ends of chromosomes. Studies in various model organisms genetically deleted for telomerase indicate that several recombination-based mechanisms also contribute to telomere maintenance. Understanding the molecular basis of these mechanisms is critical since some human tumors form without telomerase, yet the sequence is maintained at the telomeres. Recombination-based mechanisms also likely contribute at some frequency to telomere maintenance in tumors expressing telomerase. Preventing telomere maintenance is predicted to impact tumor growth, yet inhibiting telomerase may select for the recombination-based mechanisms. Telomere recombination mechanisms likely involve altered or unregulated pathways of DNA repair. The use of some DNA damaging agents may encourage the use of these unregulated pathways of DNA repair to be utilized and may allow some tumors to generate resistance to these agents depending on which repair pathways are altered in the tumors. This review will discuss the various telomere recombination mechanisms and will provide rationale regarding the possibility that L1 retrotransposition may contribute to telomere maintenance in tumors lacking telomerase.