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1 Burgers, P.M., Koonin, E.V., Bruford, E., Blanco, L., Burtis, K.C., Christman, M.F., Copeland, W.C., Friedberg, E.C., Hanaoka, F., Hinkle, D.C., Lawrence, C.W., Nakanishi, M., Ohmori, H., Prakash, L., Prakash, S., Reynaud, C.A., Sugino, A., Todo, T., Wang, Z., Weill, J.C., & Woodgate, R.J. Biol. Chem.,,. Hirose, F., Hotta, Y., Yamaguchi, M., & Matsukage, A. Exp. Cell Res.,,. Nourrit, F., Coquilleau, I., D Andon, M.F., Rougeon, F., & Doyen, N.J. Mol. Biol.,,. Dominguez, O., Ruiz, J.F., de Lera, L.T., Garcia-Diaz, M., Gonzalez, M.A., Kirchhoff, T., Martinez-A, C., Bernad, A., & Blanco, L.EMBO J.,,. Nagasawa, K., Kitamura, K., Yasui, A., Nimura, Y., Ikeda, K., Hirai, M., Matsukage, A., & Nakanishi, M.J. Biol. Chem.,,. Uchiyama, Y., Kimura, S., Yamamoto, T., Ishibashi, T., & Sakaguchi, K.Eur. J. Biochem.,,. Sakamoto, A., Iwabata, K., Koshiyama, A., Sugawara, H., Yanai, T., Kanai, Y., Takeuchi, R., Daikuhara, Y., Takakusagi, Y., & Sakaguchi, K.Chromosoma,,. Takeuchi, R., Ruike, T., Nakamura, R., Shimanouchi, K., Kanai, Y., Abe, Y., Ihara, A., & Sakaguchi, K.J. Biol. Chem.,,. Lee, J.W., Blanco, L., Zhou, T., Garcia-Diaz, M., Bebenek, K., Kunkel, T.A., Wang, Z., & Povirk, L.F.J. Biol. Chem.,,. Wilson, T.E. & Lieber, M.R.J. Biol. Chem.,,. Kimura, S. & Sakaguchi, K.Chem. Rev.,,. Dianova, I.I., Sleeth, K.M., Allinson, S.L., Parsons, J.L., Breslin, C., Caldecott, K.W., & Dianov, G.L.Nucleic Acids Res.,,. Alseth, I., Osman, F., Korvald, H., Tsaneva, I., Whitby, M.C., Seeberg, E., & Bjoras, M.Nucleic Acids Res.,,. Sugo, N., Aratani, Y., Nagashima, Y., Kubota, Y., & Koyama, H.EMBO J.,,. Nakamura, J. & Swenberg, J.A. Cancer Res.,,. Evolution and functions of X-family DNA polymerases in eukaryotes Yukinobu Uchiyama, Ryo Takeuchi, Hirofumi Kodera, and Kengo Sakaguchi Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Yamazaki, Noda, Chiba, Japan DNA ES Mario Capecchi Oliver Smithies Martin Evans http: nobelprize.org nobel_prizes medicine laureates HT HCT B Nalm- HT Andrew Porter HCT Bert Vogelstein p53 p21 Michael Lieber Nalm- LIG4 Nalm-

2 Nalm- Nalm-ALL B t q p MSH2 p53 Nalm- Nalm- Nalm- RT-PCR A UCSC Genome Browser Ensembl Genome Browser A DNA ligase IV LIG4BBLM UCSC Genome Browser GC GenBank mrna RepeatMasker snornabase mirbase non-coding RNA C BLM Ensembl Genome Browser SMART Pfam

3 B HCT UCSC Genome Browser Golden Path http: genome. ucsc.edu ORF GC A B PCR DNA kb GC PCR non-coding RNA kb A LIG4

4 C ORF LIG4 kb B BLM kb Ensembl Genome Browser http: BLM DEAD DEAH box C BLM BLM Nalm- kb A DNA PCR GC PCR UCSC Genome Browser RepeatMasker PCR

5 Nalm-

6 A B Nalm- A DT-A A Puro r Hyg r B GTE- Amaxa Nucleofector II

7 Nalm- DNA PCR loxp PCR A PCR B loxp Cre RNA RNA DT DT Nalm- DT Nalm- Nalm- Grimm, D.Science,,. Yanez, R.J. & Porter, A.C.Gene Ther.,,. Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J.P., Sedivy, J.M., Kinzler, K.W., & Vogelstein, B. Science,,. Shirasawa, S., Furuse, M., Yokoyama, N., & Sasazuki, T. Science,,. Grawunder, U., Zimmer, D., Fugmann, S., Schwarz, K., & Lieber, M.R.Mol. Cell,,. Hurwitz, R., Hozier, J., LeBien, T., Minowada, J., Gajl- Peczalska, K., Kubonishi, I., & Kersey, J.Int. J. Cancer,,. Wlodarska, I., Aventin, A., Ingles-Esteve, J., Falzetti, D., Criel, A., Cassiman, J.J., Mecucci, C., Van den Berghe, H., & Marynen, P.Blood,,. Adachi, N., So, S., Iiizumi, S., Nomura, Y., Murai, K., Yamakawa, C., Miyagawa, K., & Koyama, H.DNA Cell Biol.,,. So,S.,Adachi,N.,&Koyama,H.DNA Cell Biol.,,. Adachi, N., Kurosawa, A., & Koyama, H.Methods Mol. Biol.,,. Adachi, N. & Lieber, M.R.Cell,,. So, S., Adachi, N., Lieber, M.R., & Koyama, H.J. Biol. Chem.,,. Iiizumi, S., Nomura, Y., So, S., Uegaki, K., Aoki, K., Shibahara, K., Adachi, N., & Koyama, H.Biotechniques,,. pp. Gene targeting in cultured human cells Susumu Iiizumi and Noritaka Adachi International Graduate School of Arts and Sciences, Yokohama City University, Seto, Kanazawa-ku, Yokohama, Japan

本文／ＹＡ６０４４Ｃ

本文／ＹＡ６０４４Ｃ in vitro Iwamaru, Y., Takenouchi, T., Ogihara, K., Hoshino, M., Takata, M., Imamura, M., Tagawa, Y., Hayashi-Kato, H., Ushiki-Kaku, Y., Shimizu, Y., Okada, H., Shinagawa, M., Kitani, H., & Yokoyama, T.J.