Abstract
DNA sequences of the deletion breakpoints of 24 human T-lymphocytehprt gene mutations are reported. These independent deletions ranged in size from 18 to 15655 base pairs. Seven of the 21 in vivo mutations arose in normal adults, three in normal children, eight in radioimmunotherapy patients and three in platinum chemotherapy patients. One in vitro mutation was isolated after 93cGy radon exposure and two after 300cGy γ radiation. The breakpoints were found to be non-random and a cluster of small deletions in exon 6 is reported. Ten of the mutations has 2–5bp direct repeats at the breakpoints. There was no excess of “deletion-associated” motifs over that expected by chance. Some breakpoints do occur at consensus topoisomerase II cleavage sites and the centromeric end of a Donehower sequence occurs exactly at a telomeric breakpoint. Three mutants had breakpoints at hairpins expected by the model of Glickman and Ripley (1).
Similar content being viewed by others
Literature Cited
Glickman, B.W. and Ripley, L.S. (1984).Proc. Nat. Acad. Sci. U.S.A. 81:512–516.
Aplan, P.D., Lombardi, D.P., Ginsberg, A.M., Cossman, J., Bertness, V.L. and Kirsch, I.R. (1990).Science 250:1426–1429.
Brown, L., Cheng, J.-T., Chen, Q., Siciliano, M.J., Crist, W., Buchanan, G. and Baer, R. (1990).EMBO J. 9:3343–3351.
Cavenee, W.K., Dryja, T.P., Phillips, R.A., Benedict, W.F., Godbout, R., Gallie, B.L., Murphree, A.L., Strong, L.C. and White, R.L. (1983)Nature 305:779–784.
Cavenee, W.K., Hansen, M.F., Nordenskjold, M., Kock, E., Maumenee, I., Squire, J.A., Phillips, R.A. and Gallie, B.L. (1985).Science 228:501–503.
Den Dunnen, J.T., Grootshcolten, P.M., Bakker, E., Blonden, L.A.J., Ginjaaar, H.B., Wapenaar, M.C., van Paassen, H.M.B., van Broeckhoven, C., Pearson, P.L. and van Ommen, G.J.B. (1989).Am. J. Hum. Genet. 45:835–847.
Rodriguez, E., Sreekantaiah, C. and Chaganti, R.S. (1994).Cancer Res. 54:3398–3406.
Dryja, T.P., Rapaport, J.M., Joyce, J.M. and Petersen, R.A. (1986).Proc. Nat. Acad. Sci. U.S.A. 83:7391–7394.
Okamoto, M., Sasaki, M., Sugio, K., Sato, C., Iwama, T., Ikeuchi, T., Tonomura, A., Sasazuki, T. and Miyaki, M. (1988).Nature 331:273–277.
Rowley, J.D. (1994).Am. J. Hum. Genet. 54:403–413.
Cline, M.J. (1994).N. Engl. J. Med. 330:328–336.
Yen, P.H., Li, X.-M., Tsai, S.-P., Johnson, C., Mogandas, T. and Shapiro, L.J. (1990).Cell 61:603–610.
Henthorn, P.S., Smithies, O. and Mager, D.L. (1990).Genomics 6:226–237.
Streisinger, G., Okada, Y., Emrich, J., Newton, J., Tsugita, A., Terzaghi, E. and Inouye, M. (1966).Cold Spr. Harbor Sym. Quant. Biol. 31:77–84.
Ripley, L.S. (1982).Proc. Nat. Acad. Sci. U.S.A. 79:4128–4132.
Kudo, S. and Fukuda, M. (1989).Proc. Nat. Acad. Sci. U.S.A. 86:4619–4623.
Nicholls, R.D., Fichel-Ghodsian, N. and Higgs, D.R. (1987).Cell 49:369–378.
Rouyer, F., Simmler, M., Page, D. and Weissenbach, J. (1987).Cell 51:417–425.
Marcus, S., Hellgren, D., Lambert, B., Fällström, S.P. and Wahlström, J. (1993).Hum. Genet. 90:477–482.
Hutchinson, C.A., Hardies, S.C., Loeb, D.D., Shehee, W.R. and Edgell, M.H. (1989). InMobile DNA, (eds.), Berg, D.E. and Howe, M.M. (American Society for Microbiology, Washington DC), pp. 593–636.
Rüdiger, N.S., Gregersen, N. and Kielland-Brandt, M.C. (1995).Nuc. Acids Res. 23:256–260.
Vanin, E.F., Henthorn, P.S., Kioussis, D., Grosveld, F. and Smithies O. (1983).Cell 35:701–709.
Sperry, A.O., Blasquez, V.C. and Garrard, W.T. (1989).Proc. Nat. Acad. Sci. U.S.A. 86:5497–5501.
Fuscoe, J.C., Zimmerman, L.J., Lippert, M.L., Nicklas, J.A., O'Neill, J.P. and Albertini, R.J. (1991).Cancer Res. 51:6001–6005.
Fuscoe, J.C., Zimmerman, L.J., Harrington-Brock, K., Burnette, L., Moore, M.M., Nicklas, J.A., O'Neill, J.P. and Albertini, R.J. (1992).Mutation Res. 283:13–20.
Halligan, B.D., Davis, J.L., Edwards, K.A. and Liu, L.F. (1982).J. Biol. Chem. 257:3995–4000.
McCoubrey, W.J. and Champoux, J. (1986).J. Biol. Chem. 261:5130–5137.
Degrassi, F., De Salvia, R., Tanzarella, C. and Palitti, F. (1989).Mutation Res. 211:125–130.
Shapiro, M.A., and Weigert, M. (1987).Molec. Cell. Biol. 7:4130–4133.
Hollis, G.F., Mitchell, K.F., Battey, J., Potter, H., Taub, R., Lenoir, G.M. and Leder, P. (1984).Nature 307:752–755.
Anand, R., Boehm, C.D., Kazazian, H.H., Jr. and Vanin, E.F. (1988).Blood 72:636–641.
Kmiec, E.B. and Holloman, W.K. (1986).Cell 44:545–554.
Kmiec, E.B., Angelides, K.J. and Holloman, W. (1985).Cell 40:139–145.
Freund, A., Bichara, M. and Fuchs, R.P.P. (1989).Proc. Nat. Acad. Sci. U.S.A. 86:7465–7469.
Freund, A.M., Bichara, M. and Fuchs, R.P.P. (1990). InMutation and the Environment, (eds.) Mendelsohn, M.L. and Albertini, R.J. (Wiley-Liss, New York), Vol. Part A:Basic Mechanisms pp. 41–49.
Edwards, A., Voss, H., Rice, P., Civitello, A., Stegemann, J., Schwager, C., Zimmerman, J., Erfle, H., Caskey, C.T. and Ansorge, W. (1990).Genomics 6:593–608.
Nicklas, J.A., Hunter, T.C., O'Neill, J.P. and Albertini, R.J. (1991).Am. J. Hum. Genet. 49:267–278.
Lippert, M.J., Albertini, R.J. and Nicklas, J.A. (1995).Mutation Res. 326:39–49.
Cariello, N.F., Craft, T.R., Vrieling, H., van Zeeland, A.A., Adams, T. and Skopek, T.R. (1992).Environ. Molec. Mutagenesis 20:81–83.
Albertini, R.J., Castle, K.L. and Borcherding, W.R. (1982).Proc. Nat. Acad. Sci. U.S.A. 79:6617–6621.
O'Neill, J.P., Sullivan, L.M., Booker, J.K., Pornelos, B.S., Falta, M.T., Greene, C.J. and Albertini, R.J. (1989).Environ. Molec. Mutagenesis 13:289–293.
O'Neill, J.P., Sullivan, L.M. and Albertini, R.J. (1990).Mutation Res. 240:135–142.
Nicklas, J.A., Falta, M.T., Hunter, T.C., O'Neill, J.P., Jacobson-Kram, D., Williams, J. and Albertini, R.J. (1990).Mutagenesis 5:461–468.
Nicklas, J.A., O'Neill, J.P., Hunter, T.C., Falta, M.T., Lippert, M.J., Jacobson-Kram, D., Williams, J.R. and Albertini, R.J. (1991).Mutation Res. 250:383–396.
Perera, F.P., Motzer, R.J., Tang, D., Reed, E., Parker, R., Warburton, D., O'Neill, J.P., Albertini, R., Bigbee, W.L., Jensen, R.H., Santella, R., Tsai, W.-Y., Simon-Cereijido, G., Randall, C. and Bosl, G. (1992).Cancer Res. 52:3558–3565.
Nicklas, J.A., Hunter, T.C., O'Neill, J.P. and Albertini, R.J. (1989).Mutation Res. 215:147–160.
Nicklas, J.A., Hunter, T.C., Sullivan, L.M., Berman, J.K., O'Neill, J.P. and Albertini, R.J. (1987).Mutagenesis 2:341–347.
Gibbs, R.A., Nguyen, P.N., Edwards, A., Civitello, A.B. and Caskey, C.T. (1990).Genomics 7:235–244.
Spitzner, J.R. and Muller, M.T. (1988).Nuc. Acids Res. 16:5533–5556.
Kunkel, T.A. (1985).J. Biol. Chem.,260:5787–5796.
Dewyse, P. and Bradley, W.E.C. (1989).Som. Cell. Molec. Gen. 15:19–28.
Krawczak, M. and Cooper, D.N. (1991).Hum. Genet. 86:425–441.
Steinmetz, M., Uematsu, Y. and Lindahl, K.F. (1987).Trends Genet. 3:7–10.
Shuman, S. (1991).J. Biol. Chem. 266:1796–1803.
Hogan, A. and Faust, E.A. (1986).Molec. Cell. Biol. 6:3005–3009.
Edelmann, W., Kroger, B., Goller, M. and Horak, I. (1989).Cell 57:937–946.
Wahls, W.P., Wallace, L.J. and Moore, P.D. (1990).Cell 60:95–103.
Been, M.D., Burgess, R.R. and Champoux, J.J. (1984).Nuc. Acids Res. 12:3097–3114.
Weaver, D.T. and Depamphilis, M.L. (1982).J. Biol. Chem. 257:2075–2086.
Kariya, Y., Kato, K., Hayashizaki, Y., Himeno, S., Tarui, S. and Matsubara, K. (1987).Gene 53:1–10.
Donehower, L.A., Slagle, B.L., Wilde, M., Darlington, G. and Butel, J.S. (1989).Nuc. Acids Res. 17:699–710.
Spitzner, J.R. and Muller, M.T. (1989).J. Molec. Recog. 2:63–74.
Triglia, T., Peterson, M.G. and Kemp, D.L. (1988).Nuc. Acids Res. 16:8186–8190.
Fuscoe, J.C., Zimmerman, L.J., Harrington-Brock, K. and Moore, M.M. (1994).Carcinogenesis 15: 1463–1466.
Giver, C.R., Nelson, S.L. and Grosovsky A.J. (1993).Environ. Molec. Mutagenesis 22:138–146.
McGregor, W.G., Maher, V.M. and McCormick, J.J. (1991).Som. Cell. Molec. Gen. 17:463–469.
Rossi, A., Thijssen, J., Tates, A., Vrieling, H. and Natarajan, A. (1990).Mutation Res. 244:353–357.
Burkhart-Schultz, K., Thomas, C.B., Thompson, C.L., Strout, C.L., Brinson, E. and Jones, I.M. (1993).Environ. Health Perspect. 101:68–74.
Gibbs, R.A., Nguyen, P.N., McBride, L.J., Koepf, S.M. and Caskey, C.T. (1989).Proc. Nat. Acad. Sci. U.S.A. 86:1919–1923.
Ikehata, H., Akagi, T., Kimura, H., Akasaka, S. and Kato, T. (1989).Mol. Gen. Genet. 219:349–358.
Recio, L., Cochrane, J., Simpson, D., Skopek, T.R., O'Neill, J.P., Nicklas, J.A. and Albertini, R.J. (1990).Mutagenesis 5:505–510.
Monnat, R.J., Hackmann, A.F.M., and Chiaverotti, T.A. (1992).Genomics 13:777–787.
Morris, T. and Thacker, J. (1993).Proc. Nat. Acad. Sci. U.S.A. 90:1392–1396.
Cariello, N.F. and Skopek, T.R. (1993).J. Mol. Biol. 231:41–57.
Davidson, B.L., Tarle S.A., Palella, T.D., and Kelley, W.N. (1989).J. Clin. Invest. 84:342–346.
DiGiovanni, L., Haynes, S.R., Misra, R. and Jelinek, W.R. (1983).Proc. Nat. Acad. Sci. U.S.A. 80:6533–6537.
Langlois, S., Kastelein, J.J.P., and Hayden, M.R. (1988).Am. J. Hum. Genet. 43:60–68.
Lehrman, M.A., Russell, D.W., Goldstein, J.L. and Brown, M.S. (1987).J. Biol. Chem. 262:3354–3361.
Jagadeeswaran, P., Tuan, D., Forget, B.G. and Weissman, S.M. (1982).Nature 296:469–470.
Henthorn, P.S., Mager, D.L., Huisman, T.H.J. and Smithies, O. (1986).Proc. Nat. Acad. Sci. U.S.A. 83:5194–5198.
Ottolenghi, S. and Giglioni, B. (1982).Nature 300:770–771.
Kazazian, H.H., Jr., Wong, C., Youssoufian, H., Scott, A.F., Phillips, D.G., and Antonarakis, S.E. (1988).Nature 332:164–166.
Mager, D.L., Henthorn, P.S. and Smithies, O. (1985).Nuc. Acids Res. 13:6559–6575.
Charron, M. and Hancock, R. (1990).Biochem. 29:9531–9537.
Berger, N.A., Chatterjee, S., Schmotzer, J.A. and Helms, S.R. (1991).Proc. Nat. Acad. Sci. U.S.A. 88:8740–8743.
Boehm, T. and Rabbitts, T.H. (1989).FASEB J. 3:2344–2359.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rainville, I.R., Albertini, R.J. & Nicklas, J.A. Breakpoints and junctional regions of intragenic deletions in the HPRT gene in human T-cells. Somat Cell Mol Genet 21, 309–326 (1995). https://doi.org/10.1007/BF02257466
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02257466