Saldanha Sabita N, Andrews Lucy G, Tollefsbol Trygve O
Department of Biology, University of Alabama at Birmingham, AL 35294-1170, USA.
Eur J Biochem. 2003 Feb;270(3):389-403. doi: 10.1046/j.1432-1033.2003.03410.x.
Short strands of tandem hexameric repeats known as telomeres cap the ends of linear chromosomes. These repeats protect chromosomes from degradation and prevent chromosomal end-joining, a phenomenon that could occur due to the end-replication problem. Telomeres are maintained by the activity of the enzyme telomerase. The total number of telomeric repeats at the terminal end of a chromosome determines the telomere length, which in addition to its importance in chromosomal stabilization is a useful indicator of telomerase activity in normal and malignant tissues. Telomere length stability is one of the important factors that contribute to the proliferative capacity of many cancer cell types; therefore, the detection and estimation of telomere length is extremely important. Until relatively recently, telomere lengths were analyzed primarily using the standard Southern blot technique. However, the complexities of this technique have led to the search for more simple and rapid detection methods. Improvements such as the use of fluorescent probes and the ability to sort cells have greatly enhanced the ease and sensitivity of telomere length measurements. Recent advances, and the limitations of these techniques are evaluated. Drugs that assist in telomere shortening may contribute to tumor regression. Therefore, factors that contribute to telomere stability may influence the efficiency of the drugs that have potential in cancer therapy. These factors in relation to telomere length are also examined in this analysis.
被称为端粒的短串联六聚体重复序列位于线性染色体的末端。这些重复序列可保护染色体不被降解,并防止染色体末端连接,这种现象可能由于末端复制问题而发生。端粒由端粒酶的活性维持。染色体末端端粒重复序列的总数决定了端粒长度,端粒长度除了在染色体稳定中具有重要性外,还是正常组织和恶性组织中端粒酶活性的一个有用指标。端粒长度稳定性是影响许多癌细胞类型增殖能力的重要因素之一;因此,端粒长度的检测和估计极其重要。直到最近,端粒长度主要通过标准的Southern印迹技术进行分析。然而,该技术的复杂性促使人们寻找更简单、快速的检测方法。诸如使用荧光探针和细胞分选能力等改进极大地提高了端粒长度测量的简便性和灵敏度。本文评估了这些技术的最新进展及其局限性。有助于端粒缩短的药物可能有助于肿瘤消退。因此,影响端粒稳定性的因素可能会影响具有癌症治疗潜力的药物的疗效。在本分析中还研究了与端粒长度相关的这些因素。