2016-01-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/679730摘要：癌細胞的關鍵特色之一為具有無限的增生複製能力，為了要應因在DNA複製後，染色體端粒過短的問題，癌細胞可藉由端粒&#37238;的活化或者是端粒重組的反應機制，來維持端粒的長度。在過去的研究報導指出，約百分之十至十五的癌細胞 (又被稱為ALT型癌細胞)，主要是利用端粒重組的方式來維持端粒的長度，但至今對於端粒重組的反應機制仍然有許多未知。我們之前的研究，已闡釋同源重組在DNA修復的作用機制，特別是我們証明了參與同源重組的因子包括HOP2-MND1複合體如何調控重組反應的機轉。有趣的是最近的研究發現，HOP2-MND1複合體在ALT型癌細胞中有高度的表現，並且協助端粒重組反應的進行。這些研究發現&#21843;發了許多新的問題，例如有哪些參與同源重組的因子也特異性的參與端粒重組反應，而這些同源重組因子在端粒重組反應的功能和作用機制又是什麼 。因此在子計畫3中，我們將會有系統的鑑定並闡明同源重組因子在端粒重組反應的作用機制，更重要的是，了解同源重組在端粒重組反應的分子機轉，將有助於我們未來擬定治療ALT型癌細胞的策略。<br> Abstract: One of the key features for cancer cells is un-limited proliferative capability. To deal with the problem of telomeric shortening after DNA replication, cancer cells employ either activation of telomerase or telomere recombination to maintain the length of telomere. It has been well documented that around 10~15% cancers, known as ALT (alternative lengthening of telomeres)-type cancers, employ telomere recombination for telomere maintenance. However, the detailed mechanism of telomere recombination remains largely unexplored. Our previous study has elucidated the action mechanism of homologous recombination in DNA repair. Particularly, we demonstrated how recombination components including HOP2-MND1 complex modulate recombination reaction. Interestingly, recent studies have revealed that HOP2-MND1 complex is highly expressed in ALT-type cancers and enhances the telomere recombination. It raises interesting questions what recombination factors are specifically involved in telomere recombination, and what are their mechanistic functions during this process. Thus, the subproject 3 proposed herein aims to identify and to delineate the mechanistic actions of recombination components specifically involved in telomere recombination. Most importantly, understanding the molecular insights of recombination machinery in telomere recombination will further assist us to devise therapeutic strategies for treatment of ALT-type cancers.同源重組端粒端粒重組HOP2-MND1複合體ALT型癌症Homologous RecombinationTelomereTelomere RecombinationHOP2-MND1 complexALT-type Cancers