複製後修復可以繞過由DNA損傷引起的複製叉停滯，並防止複製叉的斷裂，因此在維持基因組完整性方面有著重要的作用。先前，我們利用次世代定序進行了轉錄組分析，來比具較順鉑抗藥性的鼻咽癌 (NPC) 細胞株HONE6和HONE15及其親代細胞株HONE1之間的表達趨勢。結果顯示，在這些具順鉑抗藥性細胞中，范可尼貧血、同源重組和複製後修復相關的基因都有高度表達。因此，我們在本篇論文進一步鑑定了HONE6和HONE15細胞，發現具順鉑抗性的HONE6和HONE15細胞株不僅對順鉑具有抗性，而且對其他DNA損傷劑，包括甲磺酸甲酯 (MMS) 和4-硝基喹啉1氧化物 (4NQO)，都有更高的抗性表現。我們還驗證了范可尼貧血、同源重組和複製後修復途徑中的數個基因，在HONE6和HONE15細胞中都有高度表達。其中，複製後修復途徑的RAD18基因，在HONE6和HONE15細胞中都高度表達，因此我們也在耗盡RAD18的細胞中確認了細胞存活率和姐妹染色體交換（SCE）的情形。意外的是，我們發現RAD18的耗竭使HONE1對MMS更加敏感，而在HONE6細胞中卻沒有觀察到此結果。另外，RAD18的耗竭會增加HONE1中的SCE，但在HONE6細胞中卻沒有表現出顯著差異。推測可能是由於HONE6細胞本來的SCE就已經有高量表現，這也就表示HONE6細胞中染色體的斷裂和重組正在不停發生。總結我們的結果表示，具化學抗性的NPC細胞會增強多種DNA修復途徑，並且這種增強作用可以促進細胞的化學抗性表型。

Post-replication repair can bypass stalled replication forks caused by DNA lesions and prevents collapse of forks, therefore playing an important role in maintenance of genome integrity. Previously, we performed transcriptome analysis to compare expression profiles between cisplatin-resistant NPC nasopharyngeal carcinoma (NPC) cell lines, HONE6 and HONE15, and their parental cell line HONE1. It revealed that Fanconi anemia (FA), homologous recombination (HR), and post-replication repair (PRR)-related genes are highly expressed in these cisplatin-resistant cells. Here, we further characterized HONE6 and HONE15 cells. We found that cisplatin-resistant HONE6 and HONE15 cell lines are not only resistant to cisplatin, but also exhibit higher resistance to other DNA damaging agents, including methyl methanesulfonate (MMS) and 4-Nitroquinoline 1-oxide (4NQO). We also verified that several genes in the FA, HR, and PRR pathways are highly expressed in HONE6 and HONE15 cells. Since RAD18 in the PRR pathway is highly expressed in HONE6 and HONE15 cells, we determined cell survival and sister chromatid exchange (SCE) in the RAD18-depleted cells. Surprisingly, the depletion of RAD18 sensitized cells to MMS in HONE1, but not in HONE6 cells. Additionally, the depletion of RAD18 increased SCE in HONE1, but showed no significant differences in HONE6 cells. It could be due to the fact that HONE6 cells have already exhibited elevated SCE, indicating that high frequency of chromosomal breaks and recombination have occurred in HONE6 cells. Our results reveal that the chemoresistant NPC cells enhance the multiple DNA repair pathways and the enhancement could contribute cells chemoresistant phenotype.

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