摘要或動機

Poly(ADP-ribose) polymerase-1 (PARP-1)是一個細胞核內的酵素，它可以被因DNA damage\r
而形成的DNA片段活化，並將NAD(+)上的ADP-ribose轉載到結合蛋白質。這些結合蛋白質對\r
於DNA的合成、DNA的修補、以及細胞週期的調控都有關係。因此，PARP-1被認為是維持基\r
因完整性的重要角色。根據初步的研究，抑制PARP-1的活性對許多疾病的治療都可能有效，\r
其中包括癌症、心臟病、中風、糖尿病、發炎以及反轉錄病毒的感染。然而，以藥物抑制一\r
個對DNA修補這麼重要的酵素會有什麼潛在的問題呢？為了要得到解答，我們需要進一步了\r
解PARP-1在DNA damage反應的機能。在這一份報告中，我製造了一個失去活性的PARP-1突變\r
種，即E988K。經過對E988K詳細的研究，我將比較及分析PARP-1野生型與E988K之間不一樣\r
的互動蛋白質，希望能對PARP-1所控制的DNA修補有更進一步的了解。\r
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Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme activated by DNA strand breaks\r
during DNA damage response and catalyzes the transfer of ADP-ribose units from the substrate NAD(+)\r
to acceptor proteins. These acceptor proteins involve in modulation of chromatin structure, DNA\r
synthesis, DNA repair, transcription, and cell cycle control. Thus, PARP-1 is believed to play an\r
important role in maintaining genome integrity through modulation of protein-protein and protein-DNA\r
interactions. PARP-1 has been the target for design of inhibitors for over twenty-five years. Inhibitors of\r
the activity of PARP-1 have been claimed to have applications in the treatment of many disease states,\r
including cancer, cardiac infarct, stroke, diabetes, inflammation and retroviral infection. However, are\r
there potential problems associated with inhibition of this DNA-repair enzyme? To answer this question,\r
we need to further understand the biological function of PARP-1 during DNA damage response. In this\r
report, an enzyme dead mutant (E988K) of PARP-1 was generated. Detailed studies of E988K show that\r
E988K could be used in the following studies. Compare and identify the different associated proteins of\r
PARP-1 wild-type and E988K will shed light into the molecular mechanism of PARP-1-mediated DNA\r
repair.