Department of Cell Biology, Physiology and Immunology, Bioscience School, Universitat Autonoma de Barcelona, Bellaterra, Spain.
Front Biosci (Landmark Ed). 2012 Jun 1;17(6):2181-96. doi: 10.2741/4044.
The nucleoprotein complexes that cap the very ends of the eukaryotic chromosomes, named telomeres, are indispensable for cell viability. Telomeric DNA shortens in each cell division until it cannot exert end-protective functions in human somatic cells. Additionally, several proteins have been described to play a key role in telomere homeostasis preventing chromosome extremities to be recognized as double-stranded breaks (DSBs). When telomeres become dysfunctional, either through excessive shortening or due to defects in the proteins that form its structure, they trigger p53/pRb pathways what limits proliferative lifespan. Impairment of telomere function together with a compromised senescence/apoptosis response leads to chromosome instability. Fusions between dysfunctional telomeres or even between dysfunctional telomeres and DSBs can initiate breakage-fusion-bridge (BFB) cycles. Initially, telomere fusions were proposed to cause only structural abnormalities. Nevertheless, changes in chromosome number have also emerged as a possible consequence of alterations in end capping. Here we review the main aspects of telomeres and telomere-based chromosome instability, highlighting why they have been proposed as a driving force for tumourigenesis.
真核染色体末端的核蛋白复合物被命名为端粒，对于细胞活力是不可或缺的。端粒 DNA 在每次细胞分裂中都会缩短，直到它不能在人类体细胞中发挥末端保护功能。此外，已经描述了几种蛋白质在端粒稳态中发挥关键作用，防止染色体末端被识别为双链断裂（DSB）。当端粒功能失调时，无论是由于过度缩短还是由于形成其结构的蛋白质缺陷，都会触发 p53/pRb 途径，从而限制增殖寿命。端粒功能的损害以及衰老/凋亡反应的受损会导致染色体不稳定。功能失调的端粒之间的融合，甚至是功能失调的端粒和 DSB 之间的融合，都可以引发断裂-融合-桥（BFB）循环。最初，端粒融合被认为只会导致结构异常。然而，染色体数目的变化也已经出现，可能是端粒末端封闭改变的结果。在这里，我们综述了端粒和基于端粒的染色体不稳定性的主要方面，强调了它们为何被提出作为肿瘤发生的驱动力。
