2019-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/653593摘要：端粒維持是染色體穩定性的先決條件，端粒&#37238;通常在DNA複製後被端粒&#37238;拉長。在缺少端粒&#37238;的人類和酵母細胞中，可以利用替代的重組途徑來維持端粒長度。然而，端粒重組的分子機制仍然有許多未知，因為此研究需具備將端粒和重組兩個專門領域的了解。為了解決這項課題，我們匯集了6位具有端粒生物學或重組機制專業知識在臺大的研究學者。因此，我們通過不同及多樣的研究策略包括酵母遺傳學，細胞學，生物化學，單分子分析和結構生物學在內的多學科方法，來探討細胞維持端粒完整性的機制。我們將特別針對：（1）端粒的細胞位置如何調控端粒重組; （2）DNA / RNA雜合體（R環）如何促進端粒重組;和（3）以生物化學、單分子、和結構面向研究端粒組成分如何與同源重組組成分有功能性的相互作用。我們的長期目標是闡釋端粒維持的分子機制，這對理解導致人類衰老的機制和對癌症潛在的治療具有重大意義。<br> Abstract: Telomere maintenance is a prerequisite for chromosome stability, and telomeres are typically elongated by telomerase following DNA replication. In both human and yeast cells that lack telomerase, telomeres are maintained via an alternative recombination pathway. However, the molecular mechanism of telomere recombination remains largely unknown due to the challenge of gathering two specialized fields, telomere and recombination, together. To meet this challenge, we have gathered together six NTU PIs with expertise in either telomere biology or recombination mechanism. As such, our consortium is completed by a multi-disciplinary approach including yeast genetics, cytology, biochemistry, single-molecule analyses, and structural biology to unravel the mechanisms of maintaining telomere integrity. We will specifically address: (1) how the cellular location of telomeres regulates telomere recombination; (2) how DNA/RNA hybrids (R-loop) promote telomere recombination; and (3) how mechanistically telomere components functionally interact with recombination machinery at biochemical, single-molecule, and structural perspectives. The long-term goal of this project is to decipher the molecular mechanism of telomere maintenance, which has significant impacts on understanding the mechanisms leading to human aging and potential therapeutic implications for cancers.端粒端粒重組R環TelomereTelomere recombinationR-loop