2016-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/643175摘要：端粒是真核細胞線性染色體末端的結構，在缺少端粒複製酵素的正常人類體細胞或酵母菌，染色體末端長度隨著每次細胞的分裂而縮短。染色體末端的逐漸縮短最終造成細胞的老化。在過程中，少數細胞可經由染色體重組的方式來維持端粒長度以逃脫老化。本實驗室之前在研究一個參與在RNA轉錄延長過程的THO複合體時，發現在沒有端粒複製酵素的情況下，THO突變造成細胞提早進入老化並伴隨著提早染色體第二型重組的發生。進一步的分析發現這現象與須要轉錄出的端粒RNA（TERRA）參與。先前的文獻已指出TERRA是端粒轉錄出未帶有轉譯功能的RNA，TERRA與端粒結合並可能參與端粒功能。我們的發現提供了一個TERRA可能參與的新功能。於此，本計畫擬針對這個可能的新功能作進一步探討，了解TERRA影響染色體重組的分子機制。酵母菌染色體第二型重組與人類細胞經由染色體重組的方式維持端粒長度極為相似，本研究成果將有助於了解人類細胞在缺少端粒複製酵素時如何以染色體重組的方式來逃脫老化。此外，TERRA是屬於一種未帶有轉譯功能的RNA，本研究將提供這類RNA一樣新穎的功能。<br> Abstract: Telomeres are the physical ends of eukaryotic linear chromosomes. In human somatic cells or yeast cells lacking telomerase, telomeres are shortened upon each cell division. This gradual shortening of telomeres eventually leads to senescence. Few surviving cells can bypass senescence through the activation of alternative recombination pathways to maintain their telomeres. Previously we identified mutations in THO complex components, which are involved in transcription-elongation and transcribed mRNA export, that triggered early senescence and type II telomere recombination in cells lacking telomerase. Our preliminary results indicate that accumulation of telomere-associated non-coding telomere repeat-containing RNA (TERRA) is required for the observed telomere effects in THO complex mutants. TERRA has been associated with telomeres and implicated in telomere function. Our results support a novel function for telomere-associated TERRA, in the form of a DNA-RNA hybrid, which triggers the formation of type II survivors. Here we propose to analyze the mechanism of how TERRA affects telomere recombination. Telomeres of the type II recombination survivors are similar to those of mammalian ALT (alternative lengthening of telomeres) cells, results generated from our research should help understanding the mechanism of generating survivors in mammalian cells lacking telomerase. Moreover, because TERRA is a long non-coding RNA, results from our proposed research should reveal a novel function for long non-coding RNA in regulating recombination.