https://scholars.lib.ntu.edu.tw/handle/123456789/564355
標題: | Tumor Cells Require Thymidylate Kinase to Prevent dUTP Incorporation during DNA Repair | 作者: | Hu C.-M. Yeh M.-T. Tsao N. Chen C.-W. Gao Q.-Z. Chang C.-Y. Lee M.-H. Fang J.-M. Sheu S.-Y. Lin C.-J. Tseng M.-C. Chen Y.-J. ZEE-FEN CHANG |
公開日期: | 2012 | 卷: | 22 | 期: | 1 | 起(迄)頁: | 36-50 | 來源出版物: | Cancer Cell | 摘要: | The synthesis of dTDP is unique because there is a requirement for thymidylate kinase (TMPK). All other dNDPs including dUDP are directly produced by ribonucleotide reductase (RNR). We report the binding of TMPK and RNR at sites of DNA damage. In tumor cells, when TMPK function is blocked, dUTP is incorporated during DNA double-strand break (DSB) repair. Disrupting RNR recruitment to damage sites or reducing the expression of the R2 subunit of RNR prevents the impairment of DNA repair by TMPK intervention, indicating that RNR contributes to dUTP incorporation during DSB repair. We identified a cell-permeable nontoxic inhibitor of TMPK that sensitizes tumor cells to doxorubicin in vitro and in vivo, suggesting its potential as a therapeutic option. ? 2012 Elsevier Inc.. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84863759637&doi=10.1016%2fj.ccr.2012.04.038&partnerID=40&md5=bb6208a02255d04f0ac71485a4b49703 https://scholars.lib.ntu.edu.tw/handle/123456789/564355 |
ISSN: | 1535-6108 | DOI: | 10.1016/j.ccr.2012.04.038 | SDG/關鍵字: | antineoplastic agent; deoxyuridine triphosphate pyrophosphatase; doxorubicin; ethyl 4 (2 (4,6 dimethyl 3 oxoisothiazolo[5,4 b]pyridin 2(3h) yl)acetyl)piperazine 1 carboxylate; histone H2AX; phosphotransferase; phosphotransferase inhibitor; ribonucleotide reductase; thymidylate kinase; unclassified drug; YMU1; animal experiment; animal model; animal tissue; antineoplastic activity; article; cancer cell; cell growth; controlled study; DNA repair; double stranded DNA break; drug sensitization; drug synthesis; enzyme binding; gene silencing; human; human cell; IC 50; in vitro study; in vivo study; mouse; nonhuman; priority journal; protein expression; tumor growth; tumor volume; tumor xenograft |
顯示於: | 分子醫學研究所 |
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