目前在癌症治療研究上遇到的一個主要障礙是，化療藥物會誘導癌細胞產生抗藥性，以本篇論文所使用的順鉑藥物(Cisplatin)而言，其為目前主要用於治療頭頸癌、肺癌、卵巢癌、膀胱癌和睾丸癌的化療藥物，Cisplatin會於DNA雙股之間(interstrand)或單股內(intrastrand)的嘌呤鹼基對(purine base)進行交聯作用(crosslink)；先前的研究發現鼻咽癌細胞會藉由同源重組(homologous recombination, HR)、模板交換(template-switching, TS)、范可尼貧血(Fanconi anemia, FA)路徑進行一連串交互作用後提高姐妹染色體交換率（Sister Chromatid Exchange, SCE），使其DNA恢復正常複製，進而導致鼻咽癌細胞產生抗藥性表現。
本篇研究針對MYST組蛋白乙醯轉移酶家族中的TIP60進行研究，MYST是由一群組蛋白乙醯轉移酶(Histone Acetyltransferase, HAT)所組成，主要參與細胞的轉錄及DNA修復作用；將具抗藥性鼻咽癌細胞(HONE6)中的TIP60基因表現抑制後，於壓力環境下其FA、HR、TS以及TLS細胞修復路徑中，許多基因表現量有明顯下降趨勢，姊妹染色體交換率也顯著下降，於細胞受損情況下觀察其DNA絲，發現複製叉停滯情況也有顯著提升，總總因素導致癌細胞的修復效率降低，進而對Cisplatin產生敏感性；最後進行染色質免疫沉澱(Chromatin immunoprecipitation, ChIP)實驗，發現TIP60會結合到調控FA及HR路徑的關鍵蛋白FAND2及BRCA1的啟動子(promoter)上。
綜觀上述結果，可以推測TIP60扮演轉錄因子的關鍵角色，藉由和DNA修復路徑相關基因的啟動子進行結合使其表現量上升，進而使癌細胞對化療藥物產生抗藥性。

Cisplatin can cause interstrand and intrastand crosslinks between purine bases and is a chemotherapeutic drug commonly used to treat cancer. However, the major obstacle for efficacy of the treatment is cisplatin resistance. We recently discovered that chronic treatment of nasopharyngeal carcinoma cells (NPC) with cisplatin induces Fanconi anemia (FA) and homologous recombination (HR) pathways to confer cisplatin resistant phenotype. The histone acetyltransferase (HATs) TIP60 is a member of the MYST family, play an important role in regulating transcription, chromatin remodeling, DNA replication, and DNA repair. Depletion of TIP60 reduces the expression of several genes in FA and HR pathways. In addition, TIP60-deficient NPC cells showing decreased sister chromatid exchange, suggesting reduced homologous recombination. Furthermore, TIP60 binds to the promoter of FANCD2 and BRCA1 by the ChIP experiment. These results suggest that TIP60 regulates the expression of FA and HR-genes, thus regulating DNA damage repair pathway, such as Fanconi anemia repair pathway and homologous recombination to confer cells the cisplatin-resistant phenotype. Targeting TIP60 could be a strategy for treating cisplatin-resistant cancer.

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