DNA拓樸酶對端粒延長重組機制的影響

DNA Topoisomerase III Involves in Telomere-Telomere Recombination Pathway

蔡宏基(Hung-Ji Tsai)

指導教授 ： 鄧述諄

國立臺灣大學/醫學院/微生物學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.00444

摘要

染色體末端會受到端粒的保護，避免染色體與染色體之間的融合；而端粒的長度需要由端粒酵素來維持，當細胞缺乏端粒酵素，端粒會逐漸的縮短而造成細胞的衰亡。少數的細胞會藉由一種端粒重組機制ALT pathway (alternative lengthening telomere)來延長端粒的長度，而讓細胞可以繼續生長。本篇研究中分別在酵母菌和人類細胞中去探討端粒複製的重組機制，早期的研究發現酵母菌中TOP3基因會關係到端粒長度的維持；我們在酵母菌中發現的確Top3p會參與在Type II端粒重組機制，一旦缺乏Top3p的活性，則會走向Type I端粒重組機制；除此之外，我們還發現Top3p-Sgs1p所存在的複合體也會共同參與在Type II端粒複製之中。基於在酵母菌中的實驗結果，我們利用siRNA成它a在人類細胞中抑制TOP3ㄘ垌OP3β的表現，結果發現TOP3ㄙ穛{的抑制在依賴重組機制延長端粒的Saos2細胞中可以成它a將ALT重組機制破壞，並且藉由未知的調控機轉將人類端粒酵素活化；而TOP3β表現的抑制則造成細胞生長遲緩且走向死亡的現象。綜觀來看，DNA拓樸酶和細胞中染色體的穩定性以及重組機制的過程有關。

關鍵字

端粒 ； 拓樸酶

並列摘要

Telomere, a special structure in the chromosome end, protects the integrity of chromosome and prevents chromosome from end-to-end fusion. Telomere maintenance depends on the reverse transcriptase, telomerase. When the activity of telomerase is missing, telomeres are shortened as cell divides. Finally, cells senescent and stop proliferating. Few cells escape the senescence and continue to proliferate through an alternative lengthening telomere (ALT) recombination pathway to maintain telomere length. In this study, we investigate telomere-telomere recombination in two model systems, budding yeast and mammalian system. We found that TOP3 was required for Type II telomere recombination pathway in budding yeast and its activity was important for telomere recombination. In addition, Sgs1p-Top3p complex cooperates in this pathway. Furthermore, siRNA system was utilized to knockdown human TOP3

並列關鍵字

TOP3 ； telomere

參考文獻

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