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Telomere structure The unusual behavior of telomeric fractions may be explained by G-G interactions. In the upper model a duplex hairpin is formed by G-G pairing. In the lower model, a G quartet(四联体) is formed when 1 G is contributed by each of 4 repeating units. Ch8 复制 复制叉 起 始 习题练习 聚合酶 合成机制 复制过程 终 止 小 结 Telomeres are synthesized by a ribonucleoprotein enzyme Telomerase(端粒酶) carries a short RNA molecule that acts as a template for the addition of the complementary DNA sequence at the 3′ end of the double helix. In the ciliate Tetrahymena(四膜虫), the DNA sequence added is TTGGGG. Ch8 复制 复制叉 起 始 习题练习 聚合酶 合成机制 复制过程 终 止 小 结 Telomerase positions itself by base pairing between the RNA template and the protruding single-stranded DNA primer. It adds G and T bases one at a time to the primer, as directed by the template. The cycle starts again when one repeating unit has been added. How telomerase works? Ch8 复制 复制叉 起 始 习题练习 聚合酶 合成机制 复制过程 终 止 小 结 Telomere -binding proteins regulate telomerase activity and telomere length Figure 8-39: Telomere-binding proteins (a) S. cerevisiae cells. Rap1 directly binds to the double stranded telomere repeat DNA, whereas Rif1 and Rif2 associate with the telomere indirectly by binding to Rap1. All three proteins have been implicated in the inhibition of telomerase activity. Cdc13 binds to the single-stranded telomere repeat DNA and is involved in telomerase recruitment. (b) Human cells. TRF1 and TRF2 bind directly to the double-stranded telomere repeat DNA. The human homolog of Rap1 as well as TIN2, TPP1, and POT1 all associate with either TRF1 or TRF2. Together these proteins form a complex that is called Shelterin for its ability to “shelter” the telomeres from the action of DNA repair enzymes. POT1 also binds directly to the single-stranded telomere repeat DNA and inhibits telomerase activity. Ch8 复制 复制叉 起 始 习题练习 聚合酶 合成机制 复制过程 终 止 小 结 Telomere length regulation by telomere-binding proteins Short telomere is bound by few
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