酶工程第二章酶生物合成的基本理论2013-3.ppt

How shelterin may shape telomeres. (A) Generation of the telomere terminus. After replication, chromosome ends require processing in order to acquire a long 3′ overhang. The nuclease involved is not known. The resulting 5′ end always has the sequence ATC-5′. When POT1 is inhibited, this precision is lost. How POT1 determines the sequence of the 5′ end is not known, but the resulting terminal structure is a preferred binding site for POT1 in vitro. (B) The t-loop structure. The 3′ overhang is strand-invaded into the adjacent duplex telomeric repeat array, forming a D-loop. The size of the loop is variable. (C) Speculative model for t-loop formation by shelterin. TRF1 has the ability to bend, loop, and pair telomeric DNA in vitro and could potentially fold the telomere. The shelterin component TRF2 can mediate t-loop formation in vitro. (D) Model for telomere length regulation by shelterin. As the t-loop is unlikely to be a substrate for telomerase, telomeres are only shown in the “open” state (either in a linear or in a more compact folded configuration) that could be generated during S phase. The presence of more shelterin on longer telomeres is proposed to increase the loading of POT1 on the telomeric overhang. POT1 bound to the 3′ end is proposed to block telomerase from acting. At the?right, short telomeres with less shelterin are shown. Due to the diminished amount of shelterin, the chance that POT1 loads on the overhang is reduced, leading to a higher chance that telomerase can elongate the telomere. Forced increase of POT1 on telomeres (through shelterin overexpression) increases the chance that telomerase will be blocked, resulting in telomere shortening. Inhibition of shelterin, or a mutant of POT1 that does not bind ssDNA, reduces the chance that telomerase will be blocked, resulting in telomere elongation. * * 能否利用抗体的这一特性将抗体开发成象酶那样的催化剂呢？ * * Myceloma骨髓瘤 spleen cell脾细胞 polyethylene glycol 聚乙二醇 propagate clone 繁殖克隆 * * 欧米伽 Ω Omega（大写Ω，小写ω?） Halve vt. 二等