2014-01-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/680114摘要：腫瘤細胞具高度的增生能力，並於此複製過程中遭受各種不同的 DNA 損傷。其中雙股 DNA 的斷裂若無法修復將會使細胞走向死亡。因此細胞須利用同源重組反應來正確的修復受損的遺傳物質。數個參與同源重組修復的蛋白已被證實與細胞癌化的過程息息相關。例如：人類 RAD51 和 RAD51AP1 的蛋白被發現高度的表達在癌化的細胞。此外我們實驗室在最近的研究闡明了另一重組酵素輔助蛋白 SWI5-SFR1 在 DNA 修復的分子機轉， 並進一步的發現 SWI5-SFR1 的蛋白亦高度的表達在腫瘤細胞。在這子計畫中，我們會進一步的研究這些重組酵素輔助蛋白在腫瘤生長過程中所扮演的角色。並期望藉由這些分子機轉的瞭解，能更進一步發展出治療因同源重組所引發的癌症。<br> Abstract: Tumor cells are highly proliferative and sustain various types of DNA damage. Among them double strand breaks (DSBs) are the most lethal chromosomal lesions, which if remain unrepaired, can lead to cell death. To deal with such lesion, cells utilize homologous recombination (HR)-mediated repair pathway to eliminate deleterious DSBs. Several recombinase accessory factors have been well documented related to tumor progression. For instance, human RAD51 and RAD51AP1 genes, which code for key components of the HR protein machinery, are frequently overexpressed in a wide variety of cancers, such as lymphoma, colorectal cancer and breast cancer. Our laboratory recently elucidated the mechanistic role of SWI5-SFR1 complex in regulating recombination process, and the preliminary results suggested both genes are overexpression in caner cells. In this proposal we will further investigate the role of those recombinase accessory factors in cancer progression. The molecular insights garnered from our study could potentially provide the basis for devising the strategies for treatment of various cancers that arise because of inappropriate HR regulation.腫瘤DNA 損傷和修復同源重組重組酵素CancerDNA damage and repairHomologous recombinationRecombinase