Mondello Chiara, Scovassi A Ivana
Istituto di Genetica Molecolare CNR, Pavia, Italy.
Biochem Cell Biol. 2004 Aug;82(4):498-507. doi: 10.1139/o04-048.
Telomeres are specialized high-order chromatin structures that cap the ends of eukaryotic chromosomes. In vertebrates, telomeric DNA is composed of repetitions of the TTAGGG hexanucleotide, is bound to a set of specific proteins, and is elongated by the reverse transcriptase enzyme telomerase. Telomerase activity is promptly detected in cells with an indefinite replicative potential, such as cancer cells, while is almost undetectable in normal cells, which are characterized by a limited life span. Mounting evidence indicates that the maintenance of telomere integrity and telomerase protect cells from apoptosis. Disruption of the telomere capping function and (or) telomerase inhibition elicit an apoptotic response in cancer cells, while restoration of telomerase activity in somatic cells confers resistance to apoptosis. The possible mechanisms linking telomeres, telomerase and apoptosis are discussed in this review, together with the impact of this field in anticancer research.
端粒是一种特殊的高阶染色质结构,位于真核染色体的末端。在脊椎动物中,端粒DNA由TTAGGG六核苷酸重复序列组成,与一组特定蛋白质结合,并由逆转录酶端粒酶延长。在具有无限复制潜能的细胞(如癌细胞)中能迅速检测到端粒酶活性,而在寿命有限的正常细胞中几乎检测不到。越来越多的证据表明,端粒完整性的维持和端粒酶可保护细胞免于凋亡。端粒帽功能的破坏和(或)端粒酶抑制会引发癌细胞的凋亡反应,而体细胞中端粒酶活性的恢复则赋予细胞抗凋亡能力。本综述讨论了端粒、端粒酶与凋亡之间可能的机制,以及该领域在抗癌研究中的影响。