分子生物学英文课件：DNA synthesis.ppt

3. Telomere and Telomerase Telomere Telomeres are the structure at the end oflinear eukaryotic chromosome. Telomere are composed of tandem repeats of G rich DNA sequence and telomere associated protein. Telomeres are necessary for chromosome maintenance and stability. Functions: ?Form protective caps on the chromosome ends ?Necessary for chromosome maintenance and stability Telomere length Telomere length varies greatly between species Telomere Length Declines 0 35 65 1,500 3,000 8,000 Age (years) Telomere length in base pairs (human white blood cells) 长 短 细胞分裂次数与端粒长短呈正比 细胞分裂 端粒阈值 端粒长短 端粒酶活 Harley (1989) 端粒的重复片段为探针检测 胎儿细胞株 婴儿细胞株 青年细胞株 老年细胞株 年龄 小 大 端粒长度 早老性侏儒症的端粒明显较正常人短 “多莉”的衰老 ＞ 研究端粒（记时器）丢失的速率/ 年，预测人类的寿命 XX XY why? PCD机制、癌细胞的无限繁殖 Telomerase An RNA-containing reverse transcriptase that using the RNA as a template, adds nucleotides to the 3 ending strand and thus prevents progressive shortening of eukaryotic linear DNA molecules during replication. Human telomerase RNA(hTR) Human telomerase associated protein 1(hTP1) Human telomerase reverse transcriptase(hTRT) Telomerase Telomerase is a specialized reverse transcriptase contains both RNA and Protein Telomerase Inchworn model How telomerase can solve the problem. In the first step,the primers are removed from the 5 ends of the daughter strands,leaving gaps.in the second step,telomerase adds extra telomeric DNA(red) to the 3 -ends of the other daughter strands.in the third step,DNA synthesis occurs,using the newly made telomeric DNA as a template.in the fourth step,the primers used in step three are removed. This leaves gaps,but the telomerase action has ensured that no net loss of DNA has occurred. Comparison of replication in prokaryotes and in eukaryotes Prokaryote Eukaryote Enzyme DNA-pol I, II, III α,β, γ, δ, ε origin single multiple Velocity (bp/sec) 2500 (fast) 250 (slowly) Total Velocity