Section of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Tex.
Transl Res. 2013 Dec;162(6):353-63. doi: 10.1016/j.trsl.2013.05.003. Epub 2013 Jun 1.
Telomeres are DNA-protein structures that form a protective cap on chromosome ends. As such, they prevent the natural ends of linear chromosomes from being subjected to DNA repair activities that would result in telomere fusion, degradation, or recombination. Both the DNA and protein components of the telomere are required for this essential function, because insufficient telomeric DNA length, loss of the terminal telomeric DNA structure, or deficiency of key telomere-associated factors may elicit a DNA damage response and result in cellular senescence or apoptosis. In the setting of failed checkpoint mechanisms, such DNA-protein defects can also lead to genomic instability through telomere fusions or recombination. Thus, as shown in both model systems and in humans, defects in telomere biology are implicated in cellular and organismal aging as well as in tumorigenesis. Bone marrow failure and malignancy are 2 life-threatening disease manifestations in the inherited telomere biology disorder dyskeratosis congenita. We provide an overview of basic telomere structure and maintenance. We outline the telomere biology defects observed in dyskeratosis congenita, focusing on recent discoveries in this field. Last, we review the evidence of how telomere biology may impact sporadic aplastic anemia and the risk for various cancers.
端粒是 DNA-蛋白质结构，形成染色体末端的保护性帽。因此，它们防止线性染色体的自然末端受到可能导致端粒融合、降解或重组的 DNA 修复活动的影响。端粒的 DNA 和蛋白质成分对于这个基本功能都是必需的，因为端粒 DNA 长度不足、末端端粒 DNA 结构丢失或关键端粒相关因子缺乏，可能会引发 DNA 损伤反应，并导致细胞衰老或凋亡。在检查点机制失效的情况下，这种 DNA-蛋白质缺陷也可能通过端粒融合或重组导致基因组不稳定。因此，正如在模型系统和人类中所显示的那样，端粒生物学缺陷与细胞和机体衰老以及肿瘤发生有关。骨髓衰竭和恶性肿瘤是遗传性端粒生物学疾病先天性角化不良中两种危及生命的疾病表现。我们提供了端粒基本结构和维持的概述。我们概述了在先天性角化不良中观察到的端粒生物学缺陷，重点介绍了该领域的最新发现。最后，我们回顾了端粒生物学如何影响特发性再生障碍性贫血和各种癌症风险的证据。
