細胞能藉由DNA修復來維持基因的完整性。鹼基切除修復程序能修復較小、非螺旋性的受損鹼基，包含那些由氧化壓力所造成的傷害。先前的研究結果以hydorxyurea和ara-C抑制DNA複製程序，8-oxoguanine的修復會受到抑制，證明氧化性DNA傷害的修補會仰賴DNA複製程序的進行。cdc45是DNA解旋酶的活化因子，在本篇的實驗中，將cdc45剔除後可證明證氧化性DNA傷害的修補需要DNA複製程序的參與。此外，geminin參與DNA複製的起始程序，將geminin剔除後發現DNA複製程序與DNA複製程序皆受到影響。由以上結果可推論DNA複製程序對氧化性DNA傷害的修補的重要性。

DNA repair is essential to genome integrity. Base excision repair (BER) is responsible to repair the small, non-helix-distorting base lesions including those induced by oxidative stress. Previous studies have suggested that repair of oxidative DNA damage depends on DNA replication. Inhibition of DNA synthesis by hydorxyurea and ara-C abolishes repair of 8-oxoguanine, a typical base lesion caused by oxidative stress. In this study, the dependence of repair of oxidative DNA damage on DNA replication is re-examined by the strategy knockdown of cdc45, the DNA helicase activator essential for DNA replication. The data of cdc45 knockdown confirm that DNA replication is essential for repair of oxidative DNA damage. In addition, knockdown of geminin, which inhibits initiation of DNA replication, was also tested. Surprisingly, the cells with geminin knockdown showed reduction of DNA replication and delay of repair of oxidative DNA damage. This effect will be discussed.

Ballabeni, A., Melixetian, M., Zamponi, R., Masiero, L., Marinoni, F., and Helin, K. (2004). Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis. The EMBO Journal 23, 3122-3132.

Bell, S.P., and Dutta, A. (2002). DNA replication in eukaryotic cells. Annual Review of Biochemistry 71, 333-374.

Bochkarev, A., Pfuetzner, R.A., Edwards, A.M., and Frappier, L. (1997). Struc-ture of the single-stranded-DNA-binding domain of replication protein A bound to DNA. Nature 9, 176-81.

Chen, M.-K., Tsai, Y.-C., Li, P.-Y., Liou, C.-C., Taniga, E.S., Chang, D.-W., M-ori, T., and Liu, Y.-C. (2011). Delay of gap filling during nucleotide excision re-pair by base excision repair: the concept of competition exemplified by the eff-ect of propolis. Toxicological Sciences 122, 339-348.

Cooke, M.S., Evans, M.D., Dizdaroglu, M., and Lunec, J. (2003). Oxidative D-NA damage: mechanisms, mutation, and disease. The FASEB Journal 17, 1195-1214.

Evans, M.D., Dizdaroglu, M., and Cooke, M.S. (2004). Oxidative DNA damag-e and disease: induction, repair and significance. Mutation Research/Reviews in Mutation Research 567, 1-61.

Fortini, P., and Dogliotti, E. (2007). Base damage and single-strand break rep-air: mechanisms and functional significance of short-and long-patch repair sub-pathways. DNA Repair 6, 398-409.

Frosina, G., Fortini, P., Rossi, O., Carrozzino, F., Raspaglio, G., Cox, L.S., Lane, D.P., Abbondandolo, A., and Dogliotti, E. (1996). Two pathways for base excision repair in mammalian cells. Journal of Biological Chemistry 271, 9573-9578.

Gratzner, H.G. (1982). Monoclonal antibody to 5-bromo-and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science 218, 474-475.

Hegde, M.L., Hazra, T.K., and Mitra, S. (2008). Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Research 18, 27-47.

Herrling, T., Jung, K., and Fuchs, J. (2006). Measurements of UV-generated free radicals/reactive oxygen species (ROS) in skin. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 63, 840-845.

Jeppesen, D.K., Bohr, V.A., and Stevnsner, T. (2011). DNA repair deficiency in neurodegeneration. Progress in Neurobiology 94, 166-200.
Kairupan, C., and Scott, R.J. (2007). Base excision repair and the role of MUTYH. Hered Cancer Clin Pract 5, 199-209.
Kiku-e, K.T., Gonzalez, M.A., Guarguaglini, G., Nigg, E.A., and Laskey, R.A. (2005). Depletion of licensing inhibitor geminin causes centrosome overduplication and mitotic defects. EMBO Reports 6, 1052-1057.

Klotz-Noack, K., McIntosh, D., Schurch, N., Pratt, N., and Blow, J.J. (2012). Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation. Journal of Cell Science 125, 2436-2445.

Klungland, A., Höss, M., Gunz, D., Constantinou, A., Clarkson, S.G., Doetsch, P.W., Bolton, P.H., Wood, R.D., and Lindahl, T. (1999). Base excision repair of oxidative DNA damage activated by XPG protein. Molecular Cell 3, 33-42.

Lan, L., Nakajima, S., Oohata, Y., Takao, M., Okano, S., Masutani, M., Wilson, S.H., and Yasui, A. (2004). In situ analysis of repair processes for oxidative DNA damage in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America 101, 13738-13743.

Liu, Y., Prasad, R., Beard, W.A., Kedar, P.S., Hou, E.W., Shock, D.D., and Wilson, S.H. (2007). Coordination of steps in single-nucleotide base excision repair mediated by apurinic/apyrimidinic endonuclease 1 and DNA polymerase β. Journal of Biological Chemistry 282, 13532-13541.

McGarry, T.J., and Kirschner, M.W. (1998). Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell 93, 1043-1053.

Mihaylov, I.S., Kondo, T., Jones, L., Ryzhikov, S., Tanaka, J., Zheng, J., Higa, L.A., Minamino, N., Cooley, L., and Zhang, H. (2002). Control of DNA replication and chromosome ploidy by geminin and cyclin A. Molecular and Cellular Biology 22, 1868-1880.

Moyer, S.E., Lewis, P.W., and Botchan, M.R. (2006). Isolation of the Cdc45/Mcm2–7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proceedings of the National Academy of Sciences 103, 10236-10241.

Murphy, M. (2009). How mitochondria produce reactive oxygen species. Biochem J 417, 1-13.

Olive, P.L., and Banáth, J.P. (2006). The comet assay: a method to measure DNA damage in individual cells. Nature protocols 1, 23-29.

Slupphaug, G., Mol, C.D., Kavli, B., Arvai, A.S., Krokan, H.E., and Tainer, J.A. (1996). A nucleotide-flipping mechanism from the structure of human uracil–DNA glycosylase bound to DNA. Nature 384, 87-92.

Tada, S., Li, A., Maiorano, D., Méchali, M., and Blow, J.J. (2001). Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nature cell biology 3, 107-113.

Takeda, D.Y., and Dutta, A. (2005). DNA replication and progression through S phase. Oncogene 24, 2827-2843.

Turrens, J.F. (2003). Mitochondrial formation of reactive oxygen species. The Journal of Physiology 552, 335-344.

Wohlschlegel, J.A., Dwyer, B.T., Dhar, S.K., Cvetic, C., Walter, J.C., and Dutta, A. (2000). Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 290, 2309-2312.

Zhu, W., and DePamphilis, M.L. (2009). Selective killing of cancer cells by suppression of geminin activity. Cancer Research 69, 4870-4877.