人细胞端粒DNA复制与长度维持

Human telomere replication and length maintenance

端粒位于染色体末端,由短的串联重复DNA片段及其结合蛋白组成。端粒在维持基因组稳定性及染色体结构完整性方面发挥着重要作用。端粒DNA由富含G/C的序列构成,包括双链区及G含量高的3'悬垂单链区(G-overhang,G-tail)。端粒DNA能够形成G四联体(G-quadruplex)和T环(T-loop)等高级结构。许多与DNA损伤修复相关的蛋白质参与端粒DNA的复制与端粒结构的维持,并相对于基因组的其他区域,端粒的DNA复制较为特别,从广义上讲,端粒DNA的复制可以包括双链复制(telomere replication),端粒酶复制延伸(telomerase extension)和C链补齐(C-rich fill-in)。端粒双链复制引起的端粒长度缩短是导致人体细胞衰老的重要原因,而端粒酶复制延伸及C链补齐是干细胞及肿瘤细胞维持其端粒长度及持续分裂能力的主要途径。端粒复制及其结构功能研究是生物医学领域的一个重要热点,阐释端粒复制的机理将为疾病预防及治疗等提供新的思路。

Telomeres are special nucleoprotein complex composed of repetitive sequence. Telomeres play important roles in chromosome integrality and genome stability. Telomeric DNA is usually G/C rich, and contains the double stranded region and G-rich single-stranded region with a 3＇-tail. In addition, telomere DNA can form G-qudruplex and T-loop structures. The replication of telomeric DNA is different from that of other genomic loci. In general, replication of telomere has three steps, including double-strand telomere DNA replication, telomerase extension and C-rich fill-in. While telomere DNA replication leads to progressive telomere shortening due to “End Replication Problem”, telomerase elongation and C-rich fill-in extend telomere, thus maintaining telomere length homeostasis in most human cancer cells and stem cells. Telomere replication is a hot spot in telomere biology, and the findings in this field will provide a new clue for disease prevention and treatment.