Instituto de Investigaciones Biomédicas CSIC/UAM, Translational Oncology Unit, Madrid, Spain.
Clin Transl Oncol. 2009 Nov;11(11):711-4. doi: 10.1007/s12094-009-0432-9.
Telomeres from most eukaryotes are composed of repeats of guanine-rich sequences whose main function is to preserve the end of the chromosomes. Telomeres are synthesised by a reverse transcriptase enzyme, telomerase (TERT), which forms part of a ribonucleoprotein complex containing also a RNA template molecule (TERC) and dyskerin. Exhaustion of telomeres during cell divisions triggers a DNA damage response that induces a senescence phenotype. The DNA damage machinery plays an essential role in maintaining the integrity of the genome and also detecting telomere shortening. However in some syndromes that involved mutations either in the telomerase complex genes or those involved in maintaining DNA secondary structure, such as the recQ helicase WRN, a higher frequency in the development of different types of malignancies is observed. We here describe the biology of some of these diseases, together with the molecular modifications in the telomerase complex genes and the impact of these alterations on the development of particular types of cancer.
大多数真核生物的端粒由富含鸟嘌呤的序列重复组成，其主要功能是保护染色体的末端。端粒由一种逆转录酶酶端粒酶（TERT）合成，端粒酶是一种核糖核蛋白复合物的一部分，该复合物还包含一个 RNA 模板分子（TERC）和 dyskerin。在细胞分裂过程中端粒的消耗会触发 DNA 损伤反应，从而诱导衰老表型。DNA 损伤机制在维持基因组完整性和检测端粒缩短方面发挥着重要作用。然而，在一些涉及端粒酶复合物基因或涉及维持 DNA 二级结构的基因突变的综合征中，例如解旋酶 WRN，观察到不同类型恶性肿瘤的发展频率更高。我们在这里描述了其中一些疾病的生物学特性，以及端粒酶复合物基因的分子改变，以及这些改变对特定类型癌症发展的影响。
