4第四章-DNA的复制.ppt

* a gradual shorting of the chromosomes Genetic information could be lost from the DNA. To overcome this, the end of eukaryotic chromosomes (telomeres) consists of hundreds of copies of a simple, noninformational repeat sequence with the 3’ end overhanging the 5’ end. * With circular DNAs, there is no problem filling all gaps because another DNA 3’- end is always upstream to serve as primer. 真核生物如何解决末端复制的问题? * Genetic information could be lost from the DNA. To overcome this, the end of eukaryotic chromosomes (telomeres) consists of hundreds of copies of a simple, noninformational repeat sequence with the 3’ end overhanging the 5’ end. 通式：Cn（A/T）m n?1，m=1-4 Telomere DNA sequence varies from one species to another. * * 染色体末端稳定性问题 √ 染色体末端融合 √ 染色体末端隐缩问题 ？ * 美国科学家伊丽莎白·布莱克本、卡萝尔·格雷德和杰克·绍斯塔克 在1984年CW.Greider和EH.Blackburn发现将一段单链的末端寡聚核苷酸加至四膜虫的提取物中后，端粒的长度延长了，这就说明了切实有这样的一种酶存在，她们将它命名为“端粒酶 1939年，Barbara McClintock发现玉米细胞的染色体断裂末端容易融合 1972年, James Watson（因为发现DNA双螺旋结构获得诺奖）最早就明确指出了这个末端隐缩问题 1978年，报道四膜虫的端粒序列1982年，端粒的发现导致人工染色体的发明1984年，报道酵母的端粒序列1985年，报道四膜虫的端粒酶活性1989年，报道四膜虫端粒酶的RNA亚基1994年，报道酵母端粒酶的RNA亚基1995年，报道酵母端粒酶活性1996年，纯化了四膜虫端粒酶的催化亚基,遗传筛选到酵母端粒酶的催化亚基1997年，证明了四膜虫和酵母端粒酶的催化亚基 * We do not know how the complementary (CA-rich) strand of the telomere is assembled but we may speculate that it could be synthesized by using the 3-OH of a terminal GT hairpin as a primer for DNA synthesis(it is not the only one, see the next slide). The exact sequence of telomere may be irrelevant. all is required is for the end to be recognized as a suitable substrate for addition. e.g.in yeast, telomeric repeats are added onto the ends fo the Tetrahymena repeats. A telomere is species-specific, In Tetrahymena, it is TTGGGG/AACCCC; In vertebrates, including humans, it is TTAGGG/AATCCC. Elizabeth Blackburn made a clever choice of organism in which to search for telomerase activity: Tetrahymena. Tetrahymena cells have many more telomeres than human cells. Because Tetrahymena has two