Skip to main content

Regulation of the cell cycle following DNA damage in normal and Ataxia telangiectasia cells

Experientia volume 52, pages 316–328 (1996)Cite this article

Abstract

A proportion of the population is exposed to acute doses of ionizing radiation through medical treatment or occupational accidents, with little knowledge of the immedate effects. At the cellular level, ionizing radiation leads to the activation of a genetic program which enables the cell to increase its chances of survival and to minimize detrimental manifestations of radiation damage. Cytotoxic stress due to ionizing radiation causes genetic instability, alterations in the cell cycle, apoptosis, or necrosis. Alterations in the G1, S and G2 phases of the cell cycle coincide with improved survival and genome stability. The main cellular factors which are activated by DNA damage and interfere with the cell cycle controls are: p53, delaying the transition through the G1-S boundary; p21WAF1/CIPI, preventing the entrance into S-phase; proliferating cell nuclear antigen (PCNA) and replication protein A (RPA), blocking DNA replication; and the p53 variant protein p53as together with the retinoblastoma protein (Rb), with less defined functions during the G2 phase of the cell cycle. By comparing a variety of radioresistant cell lines derived from radiosensitive ataxia talangiectasia cells with the parental cells, some essential mechanisms that allow cells to gain radioresistance have been identified. The results so far emphasise the importance of an adequate delay in the transition from G2 to M and the inhibition of DNA replication in the regulation of the cell cycle after exposure to ionizing radiation.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Barak, Y., Juven, T., Haffner, R., and Oren, M., mdm2 expression is induced by wildtype p53 activity. EMBO J.12 (1993) 461–468.

    PubMed  Google Scholar 

  2. Bates, P. R., and Lavin, M. F., Comparison of gamma-radiation-induced accumulation of ataxia telangiectasia and control cells in G2 phase. Mutat. Res.218 (1989) 165–170.

    PubMed  Google Scholar 

  3. Beamish, H., Khanna, K. K., and Lavin, M. F., Ionizing radiation and cell cycle progression in ataxia telangiectasia. Radiat. Res.138 (1994) 130–133.

    Google Scholar 

  4. Beamish, H., and Lavin, M. F., Radiosensitivity in ataxiatelangiectasia: anomalies in radiation-induced cell cycle delay. Int. J. Radiat. Biol.65 (1994) 175–184.

    PubMed  Google Scholar 

  5. Becker, Y., Asher, Y., and Tabor, E., Transfection of SV40-transformed ataxia-telangiectasia fibroblasts with mouse DNA corrects hypersensitivity to neocarzinostatin and activates fibronectin gene expression. Israel J. med. Sci.28 (1992) 837–847.

    PubMed  Google Scholar 

  6. Bischoff, F. R., and Ponstingl, H., Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature, Lond.354 (1991) 80–82.

    Google Scholar 

  7. Bischoff, F. Z., Yim, S. O., Pathak, S., Grant, G., Siciliano, M. J., Giovanella, B. C., Strong, L. C., and Tainsky, M. A., Spontaneous abnormalities in normal fibroblasts from patients with Li-Fraumeni cancer syndrome: aneuploidy and immortalization. Cancer Res.50 (1990) 7979–7984.

    PubMed  Google Scholar 

  8. Brach, M. A., Hass, R., Sherman, M. L., Gunji, H., Weichselbaum, R., and Kufe, D. W., Ionizing radiation induces expression and binding activity of the nuclear factor kappa-B. Clin. Invest.88 (1991) 691–695.

    Google Scholar 

  9. Brill, S. J., and Stillman, B., Yeast replication factor-A functions in the unwinding of the SV40 origin of DNA replication. Nature, Lond.342 (1989) 92–95.

    Google Scholar 

  10. Bryant, P. E., Enzymatic restriction of mammalian cell DNA: evidence for double-strand breaks as potentially lethal lesions. Int. J. Radiat. Biol.48 (1985) 55–60.

    Google Scholar 

  11. Bundey, S., Clinical and genetic features of ataxiatelangiectasia. (Review). Int. J. Radiat. Biol.66 (1994) S23-S31.

    PubMed  Google Scholar 

  12. Canman, C. E., Wolff, A. C., Chen, C-Y., Fornace, A. J., and Kastan, M. B., The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia. Cancer Res.54 (1994) 5054–5058.

    PubMed  Google Scholar 

  13. Chellappan, S. P., Hiebert, S., Mudryj, M., Horowitz, J. M., and Nevins, J. R., The E2F transcription factor is a cellular target for the RB protein. Cell65 (1991) 1053–1061.

    PubMed  Google Scholar 

  14. Chen, C., Oliner, J. D., Zhan, Q., Fornace, A. Jr., Vogelstein, B., and Kastan, M. B., Interactions between p53 and MDM2 in a mammalian cell cycle chekpoint pathway. Proc. natl Acad. Sci. USA91 (1994) 2684–2688.

    PubMed  Google Scholar 

  15. Chen, P., Kidson, C., and Lavin, M., Evidence of different complementation groups amongst human genetic disorders characterized by radiodensitivity. Mutat. Res.285 (1993) 69–77.

    PubMed  Google Scholar 

  16. Chen, P., Farrell, A., Hobson, K., Girjes, A., and Lavin, M., Comparative study of radiation-induced G2 phase delay and chromatid damage in families with ataxia telangiectasia. Cancer Genet. Cytogenet.76 (1994) 43–46.

    PubMed  Google Scholar 

  17. Chen, P., Girges, A., Hobson, K., Beamich, H., Khanna, K. K., Farrell, A., Gatei., M., Teale, B., and Lavin, M. F., Genetic complementation of radiosensitivity by 3′ untranslated regions (UTR) of RNA, in press (1996).

  18. Clarke, A. R., Purdie, C. A., Harrison, D. J., Morris, R. G., Bird, C. C., Hooper, M. L., and Wyllie, A. H., Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature Lond.362 (1993) 849–852.

    PubMed  Google Scholar 

  19. Cornforth, M. N., and Bedford, J. S., On the nature of a defect in cells from individuals with ataxia-telangiectasia. Science227 (1985) 1589–1591.

    PubMed  Google Scholar 

  20. Cox, R., Masson, W. K., Weichselbaum, R. R., Nove, J., and Little, J. B., The repair of potentially lethal damage in x-irradiated cultures of normal and ataxia telangiectasia human fibroblasts. Int. J. Radiat. Biol.39 (1981) 357–365.

    Google Scholar 

  21. Datta, R., Rubin, E., Sukhatme, V., Qureshi, S., Hallahan, D. E., Weichselbaum, R. R., and Kufe, D., Ionizing radiation activates transcription of the EGR-1 gene via CArG elements. Proc. natl Acad. Sci. USA89 (1992) 10149–10153.

    PubMed  Google Scholar 

  22. Day, R. S., Ziolkowski, C. H. J., Schuderio, D. A., Meyer, S. A., Lubeniecki, A. S., Girardi, A. J., Galloway, S. M., and Bynum, G. D., Defective repair of alkylated DNA by human tumour and SV40-transformed human cell strains. Nature, Lond.288 (1980) 724–727.

    Google Scholar 

  23. Demarcq, C., Bunch, R. T., Creswell, D., and Eastman, A., The role of cell cycle progression in cisplatin-induced apoptosis in Chinese hamster ovary cells. Cell Growth Diff.5 (1994) 983–993.

    PubMed  Google Scholar 

  24. Denekamp, J., Cell kinetics and radiation biology. Int. J. Radiat. Biol.49 (1986) 357–380.

    Google Scholar 

  25. Devoto, S. H., Mudryj, M., Pines, J., Hunter, T. and Nevins, J. R., A cyclin-A-protein kinase complex possesses sequencespecific DNA binding activity: p33cdk2 is a component of the E2F-cyclin-A complex. Cell68 (1992) 167–176.

    PubMed  Google Scholar 

  26. Din, S. U., Brill, S. J., Fairman, M. P., and Stillman, B., Cell-cycle-regulated phosphorylation of DNA replication factor A from human and yeast cells. Genes Devl.4 (1990) 968–977.

    Google Scholar 

  27. Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A. Jr., Butel, J. S., and Bradley, A., Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature, Lond.356 (1992) 215–221.

    Google Scholar 

  28. Dunaief, J. L., Strober, B. E., Guha, S., Khavari, P. A., Alin, K., Luban, J., Begemann, M., Crabtree, G. R., and Goff, S. P., The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell79 (1994) 119–130.

    PubMed  Google Scholar 

  29. Dulic, V., Kaufmann, W. K., Wilson, S. J., Tlsty, T. D., Lees, E., Harper, J. W., Elledge, S. J., and Reed, S. I., p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell76 (1994) 1013–1023.

    PubMed  Google Scholar 

  30. Dutta, A., and Stilman, B.,cdc2 family kinases phosphorylate a human cell DNA replication factor, RPA, and activate DNA replication. EMBO J.11 (1992) 2189–2199.

    PubMed  Google Scholar 

  31. Duvall, E., and Wyllie, A. H., Death and the cell. Immunol. Today7 (1986) 115–119.

    Google Scholar 

  32. El-Deiry, W., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., and Vogelstein, B., WAFI, a potential mediator of p53 tumor suppression. Cell75 (1993) 817–825.

    PubMed  Google Scholar 

  33. El-Deiry, W. S., Harper, J. W., O'Conner, P. M., Velculescu, V. E., Canman, C. E., Jackman, J., Pietenpol, J. A., Burrell, M., Hill, D. E., Wang, Y., Wiman, K. G., Mercer, E. W., Kastan, M. B., Kohn, K. W., Elledge, S. J., Kinzler, K. W., and Vogelstein, B., WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res.54 (1994) 1169–1174.

    PubMed  Google Scholar 

  34. Enoch, T., and Nurse, P., Coupling M phase and S phase: controls maintaining the dependance of mitosis on chromosome replication. Cell65 (1991) 921–923.

    PubMed  Google Scholar 

  35. Erdile, L. F., Heyer, W. D., Kolodner, R., and Kelly, T. J., Characterization of a cDNA encoding the 70-kDa singlestranded DNA-binding subunit of human replication protein A and the role of the protein in DNA replication. J. biol. Chem.266 (1991) 12090–12098.

    PubMed  Google Scholar 

  36. Fairman, M. P., and Stillman, B., Cellular factors required for multiple stages of SV40 DNA replicationin vitro. EMBO J.7 (1988) 1211–1218.

    PubMed  Google Scholar 

  37. Fang, F., and Newport, J. W., Evidence that the G1-S and G2-M transitions are controlled by differentcdc2 proteins in higher eukaryotes. Cell66 (1991) 731–742.

    PubMed  Google Scholar 

  38. Fields, S., and Jang, S. K., Presence of a potent transcription activating sequence in the p53 protein. Science249 (1990) 1046–1049.

    PubMed  Google Scholar 

  39. Fornace, A. J., Nebert, D. W., Hollander, M. C., Luethy, J. D., Papathanasiou, M., Fargnoli, J., and Holbrook, N. J., Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents. Molec. cell. Biol.9 (1989) 4196–4203.

    PubMed  Google Scholar 

  40. Frankenberg, D., Frankenberg-Schwager, M., Blocher, D., and Harbich, R., Evidence for DNA double strand treaks as the critical lesions in yeast cells irradiated with sparsely or densely ionizing radiation under oxic or anoxic conditions. Radiat. Res.88 (1981) 524–532.

    PubMed  Google Scholar 

  41. Fukunaga, N., Burrows, H. L., Meyers, M., Schea, R. A., and Boothman, D. A., Enhanced induction of tissue-type plasminogen activator in normal human cells compared to cancer-prone cells following ionizing radiation. Int. J. Radiat Oncol. Biol. Phys.24 (1992) 949–957.

    PubMed  Google Scholar 

  42. Fulop, G. M., and Phillips, R. A., The scid mutation in mice causes a general defect in DNA repair. Nature, Lond.347 (1990) 479–482.

    Google Scholar 

  43. Ganesh, A., North, P., and Thacker, J., Repair and misrepair of site-specific DNA double strand breaks by human cell extracts. Mutat. Res.299 (1993) 251–259.

    PubMed  Google Scholar 

  44. Gatti, R. A., Boder, E., Vinters, H. V., Sparkes, R. S., Norman, A., and Lange, K., Ataxia-telangecietasia: an interdisciplinary approach to pathogenesis. Medicine70 (1991) 99–117.

    PubMed  Google Scholar 

  45. Gatti, R. A., Lange, E., Rotman, G., Chen, X., Uhrhammer, N., Liang, T., Chiplunkar, S., Yang, L., Udar, N., Dandekar, S., Sheikhavandi, S., Wang, Z., Yang, H.-M., Polikow, J., Elashoff, M., Teletar, M., Sanal, O., Chessa, L., McConville, C., Taylor, M., Shiloh, Y., Porras, O., Borresen, A.-L., Wegner, R.-D., Curry, C., Gerken, S., Lange, K., and Concannon, P., Genetic haplotyping of ataxia-telangiectasia families localizes the major gene to an ∼ 850 kb region on chromosome 11q23. 1. Int. J. Radiat. Biol.66 (1994) 57–63.

    Google Scholar 

  46. Gekeler, V., Wilisch, A., Probst, G., Kugel, A., Brischwein, K., Engelcke, M., and Probst, H., Staurosporine suppresses replicon initiation in mammalian cells. FEBS Lett.327 (1993) 150–156.

    PubMed  Google Scholar 

  47. Ginsberg, D., Mechta, F., Yaniv, M., and Oren, M., Wildtype p53 can down-modulate the activity of various promoters. Proc. natl Acad. Sci. USA88 (1991) 9979–9983.

    PubMed  Google Scholar 

  48. Girard, F., Strausfeld, U., Fernandez, A. and Lamb, N. J., Cyclin-A is required for the onset of DNA replication in mammalian fibroblasts. Cell67 (1991) 1169–1179

    PubMed  Google Scholar 

  49. Hallahan, D. E., Sukhatme, V. P., Sherman, C. M. L., Virudachalam, S., Kufe, D., and Weichselbaum, R. R., Protein kinase mediates X-ray inducibility of nuclear signal transduces EGR-1 and JUN. Proc. natl Acad. Sci. USA88 (1991) 2156–2160.

    PubMed  Google Scholar 

  50. Hand, R., and Gautschi, J. R., Replication of mammalian DNA in vitro. Evidence for initiation from fiber autoradiography. J. cell. Biol.82 (1979) 485–493.

    PubMed  Google Scholar 

  51. Harnden, D. G., The nature of ataxia-telangiectasia: problems and perspectives. Int. J. radiat. Biol.66 (1994) S13-S19.

    PubMed  Google Scholar 

  52. Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K., and Elledge, S. J., The p21 CdK-interacting protein Cip1 is a potent inhibitor of G1 cyclin dependent kinases. Cell75 (1993) 805–816.

    PubMed  Google Scholar 

  53. Harper, K. S., Lorimore, S. A., and Wright, E. G., Delayed appearance of radiation-induced mutations at the Hprt locus in murine haemopoietic cells. Submitted (1995).

  54. Hartwell, L. H., and Weinert, T. A., Checkpoints: controls that ensure the order of cell cycle events. Science246 (1989) 629–634.

    PubMed  Google Scholar 

  55. Heichman, K. A., and Roberts, J. M., Rules to replicate by. Cell79 (1994) 557–562.

    PubMed  Google Scholar 

  56. Hittelman, W. N., and Pandita, T. K., Possible role of chromatin alteration in the radiosensitivity of ataxia-telangiectasia. Int. J. Radiat. Biol.66 (1994) S109-S113.

    PubMed  Google Scholar 

  57. Holmberg, K., Falt, S., Johansson, A., and Lambert, B., Clonal chromosome aberrations and genomic instability in X-irradiated human T-lymphocyte cultures. Mutat. Res.286 (1993) 321–330.

    PubMed  Google Scholar 

  58. Hong, J. H., Gatti, R. A., Huo, Y. K., Chiang, C. S., and McBride, W. H., G2/M-phase arrest and release in ataxia telangiectasia and normal cells after exposure to ionizing radiation. Radiat. Res.140 (1994) 17–23.

    PubMed  Google Scholar 

  59. Houldsworth, J., Cohen, D., Singh, S., and Lavin, M. F., The response of ataxia-telangiectasia lymphoblastoid cells to neutron irradiation. Radiat. Res.125 (1991) 277–282.

    PubMed  Google Scholar 

  60. Hsieh, C. L., Arlett, C. F., and Lieber, M. R., V(D)J recombination in ataxia-telangiectasia, Bloom's syndrome and a DNA ligase I-associated immunodeficiency disorder. J. biol. Chem.268 (1993) 20105–20109.

    PubMed  Google Scholar 

  61. Hupp, T. R., Meck, D. W., Midgley, C. A., and Lane, D. P., Regulation of the specific DNA binding function of p53. Cell71 (1992) 875–886.

    PubMed  Google Scholar 

  62. Imray, F. P., and Kidson, C., Perturbations of cell-cycle progression in gamma-irradiated ataxia-telangiectasia and Huntington's disease cells detected by DNA flow cytometric analysis. Mut. Res.112 (1983) 369–382.

    Google Scholar 

  63. Ishizaki, K., Ejima, Y., Matsunaga, T., Hara, R., Sakamoto, A., Ikenaga, M., Ikawa, Y., and Aizawa, S., Increased UV-induced SCEs but normal repair of DNA damage in p53 deficient mouse cells. Int. J. Cancer58 (1994) 254–257.

    PubMed  Google Scholar 

  64. Jacobs, T., Control of the cell cycle. Devel. Biology153 (1992) 1–15.

    Google Scholar 

  65. Jaspers, N. G., and Bootsma, D., Genetic heterogeneity in ataxia-telangiectasia studied by cell fusion. Proc. natl Acad. Sci. USA79 (1982) 2641–2644.

    PubMed  Google Scholar 

  66. Jaspers, N. G., Gatti, R. A., Baan, C., Linssen, P. C., and Bootsma, D., Genetic complementation analysis of ataxia telangiectasia and Nijmegen breakage syndrome: a survey of 50 patients. Cytogenet. Cell Genet.49 (1988) 259–263.

    PubMed  Google Scholar 

  67. Jeggo, P. A., Tesmer, J., and Chen, D. J., Genetic analysis of ionizing radiation sensitive mutants of cultured mammalian cell lines. Mut. Res.254 (1991) 125–133.

    Google Scholar 

  68. Kadhim, M. A., MacDonald, D. A., Goodhead, D. T., Lorimore, S. A., Marsden, S. J., and Wright, E. G., Transmission of chromosomal instability after plutonium alphaparticle irradiation. Nature, Lond.355 (1992) 738–740.

    Google Scholar 

  69. Kapp, L. N., and Painter, R. B., Stable radioresistance in ataxia-telangiectasia cells containing DNA from normal human cells. Int. J. Radiat. Biol.56 (1989) 667–675.

    PubMed  Google Scholar 

  70. Karantza, V., Maroo, A., Fay, D., and Sedivy, J. M., Overproduction of Rb protein after the G1/S boundary causes G2 arrest. Molec. cell. Biol.13 (1993) 6640–6652.

    PubMed  Google Scholar 

  71. Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B., and Craig, R. W., Participation of p53 protein in the cellular response to DNA damage. Cancer Res.51 (1991) 6304–6311.

    PubMed  Google Scholar 

  72. Kastan, M. B., Zhan, Q., el-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., Plunkett, B. S., Vogelstein, B., and Fornace, A. J. Jr., A mammalian cell cycle checkpoint pathway utilizing p53 and gadd45 is defective in ataxia-telangiectasia. Cell71 (1992) 587–597.

    PubMed  Google Scholar 

  73. Kaufmann, W. K., Boyer, J. C., Estabrooks, L. L., and Wilson, S. J., Inhibition of replicon initiation in human cells following stabilization of topoisomerase-DNA cleavable complexes. Molec. cell. Biol.11 (1991) 3711–3718.

    PubMed  Google Scholar 

  74. Khanna, K. K., and Lavin, M. F., Ionizing radiation and UV induction of p53 protein by different pathways in ataxiatelangiectasia cells. Oncogene8 (1993) 3307–3312.

    PubMed  Google Scholar 

  75. King, R. W., Jackson, P. K., and Kirschner, M. W., Mitosis in transition. Cell79 (1994) 547–550

    PubMed  Google Scholar 

  76. Kirsch, I. R., V(D)J recombination and ataxia-telangiectasia: (Review). Int. J. Radiat. Biol.66 (1994) S97-S108.

    PubMed  Google Scholar 

  77. Komatsu, K., Kodama, S., Okumura, Y., Koi, M., and Oshimura, M., Restoration of radiation resistance in ataxiatelangiectasia cells by the introduction of normal human chromosome 11. Mut. Res.235 (1990) 59–63.

    Google Scholar 

  78. Komatsu, K., Yoshida, M., and Okumura, Y., Murine Scid cells complement ataxia-telangiectasia cells and show a normal post-irradiation response of DNA synthesis. Int. J. Radiat. Biol.63 (1993) 725–730.

    PubMed  Google Scholar 

  79. Kuerbitz, S. J., Plunkett, B. S., Walsh, W. V., and Kastan, M. B., Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc. natl Acad. Sci. USA89 (1992) 7491–7495.

    PubMed  Google Scholar 

  80. Kysela, B. P., Michael, B. D., and Arrand, J. E., Relative contributions of levels of initial DNA damage and repair of double-strand breaks to the ionizing radiation-sensitive phenotype of the chinese hamster cell mutant XR-V15B. Part I X-rays. Int. J. Radiat. Biol.63 (1993) 609–616.

    PubMed  Google Scholar 

  81. Kysela, B. P., Lohrer, H. D., and Arrand, J. E., Defects in the kinetics of DNA double-strand break repair and inhibition of DNA synthesis in the ataxia telangiectasia AT5BI-VA cell line: comparison to a corrected hybridatxbc. Radiat. Res.144 (1995) 276–281.

    PubMed  Google Scholar 

  82. Laitha, L. G., Oliver, R., Berry, R., and Noyes, W. D., Mechanism of radiation effect on the progress of synthesis of deoxyribonucleic acid. Nature, Lond.182 (1958) 1788–1790.

    Google Scholar 

  83. Lambert, C., Schultz, R. A., Smith, M., Wagner-McPherson, C., McDaniel, L. D., Donlon, T., Stanbridge, E. J., and Friedberg, E. C., Functional complementation of ataxiatelangiectasia group D (AT-D) cells by microcell-mediated chromosome transfer and mapping of the AT-D locus to the region 11q22–23. Proc. natl Acad. Sci. USA88 (1991) 5907–5911.

    PubMed  Google Scholar 

  84. Larner, J. M., Lee, H., and Hamlin, J. L., Radiation effects on DNA synthesis in a defined chromosomal replicon. Molec. cell. Biol.14 (1994) 1901–1908.

    PubMed  Google Scholar 

  85. Lavin, M. F., Le-Poidevin, P., and Bates, P., Enhanced levels of radiation-induced G2 phase delay in ataxia telangiectasia heterozygotes. Cancer Genet. Cytogenet.60 (1992) 183–187.

    PubMed  Google Scholar 

  86. Lee, J. M. and Bernstein, A., p53 mutations increase resistance to ionizing radiation. Proc. natl Acad. Sci. USA90 (1993) 5742–5746.

    PubMed  Google Scholar 

  87. Lees, J. A., Buchkovich, K. J., Marshak, D. R., Anderson, C. W., and Harlow, E., The retinoblastoma protein is phosphorylated on multiple sites by human cdc2. EMBO J.10 (1991) 4279–4290.

    PubMed  Google Scholar 

  88. Lehmann, A. R., Arlett, C. F., Burke, J. F., Green, M. H., James, M. R., and Lowe, J. E., A derivative of an ataxiatelangiectasia (A-T) cell line with normal radiosensitivity but A-T-like inhibition of DNA synthesis. Int. J. Radiat. Biol.49 (1986) 639–643.

    Google Scholar 

  89. Lett, J. T., Caldwell, I., Dean, C. J., and Alexander, P., Rejoining of x-ray induced breaks in the DNA of leukaemia cells. Nature, Lond.214 (1967) 790–792.

    Google Scholar 

  90. Li, R., Waga, S., Hannon, G. J., Beach, D., and Stillman, B., Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature, Lond.371 (1994) 534–537.

    Google Scholar 

  91. Little, J. B., Delayed initiation of DNA synthesis in irradiated human diploid cells. Nature, Lond.218 (1968) 1064–1065.

    Google Scholar 

  92. Liu, N., and Bryant, P. E., Response of ataxia telangiectasia cells to restriction endonuclease induced DNA double-strand breaks: I. Cytogenetic characterization. Mutagenesis8 (1993) 503–510.

    PubMed  Google Scholar 

  93. Liu, V. F., and Weaver, D. T., The ionizing radiation-induced replication protein A phosphorylation response differs between ataxia telangiectasia and normal human cells. Molec. cell. Biol.13 (1993) 7222–7231.

    PubMed  Google Scholar 

  94. Lock, R. B., and Ross, W. E., Possible role for p34cdc2 kinase in etoposide-induced cell death of Chinese hamster ovary cells. Cancer Res.50 (1990) 3767–3771.

    PubMed  Google Scholar 

  95. Lohrer, H. D., Tangen, U., Anderson, R. F., and Arrand, J. E., Characterization of a hybrid hamster-human cell line complemented for the ataxia-telangiectasia DNA repair defects. Pathobiology62 (1994) 140–148.

    PubMed  Google Scholar 

  96. Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., and Jacks, T., p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature, Lond.362 (1993) 847–849.

    Google Scholar 

  97. Lu, X., and Lane, D. P., Differential induction of transeriptionally active p53 following UV or ionizing radiation: defects in chromosome instability syndromes? Cell75 (1993) 765–778.

    PubMed  Google Scholar 

  98. Lücke-Huhle, C., Alterations in oncogene expression and radiosensitivity in the most frequently used SV40-transformed human skin fibroblasts. Int. J. Radiat. Biol.65 (1994) 665–673.

    PubMed  Google Scholar 

  99. Maity, A., McKenna, W. G., and Muschel, R., The molecular basis for cell cycle delays following ionizing radiation: a review. Radiotherapy Oncology31 (1994) 1–13.

    Google Scholar 

  100. Makino, F., and Okada, S., Effects of ionizing radiation on DNA replication in cultured mammalian cells. Radiat. Res.62 (1975) 37–51.

    PubMed  Google Scholar 

  101. McConville, C. M., Byrd, P. J., Ambrose, H. J., and Taylor, A. M. R., Genetic and physical mapping of the ataxia-telangiectasia locus on chromosome 11q22–23 (Review). Int. J. Radiat. Biol.66 (1994) S45-S57.

    PubMed  Google Scholar 

  102. Meyn, M. S., High spontaneous intrachromosomal recombination rates in ataxia-telangiectasia. Science260 (1993) 1327–1330.

    PubMed  Google Scholar 

  103. Meyn, M. S., Lu-Kuo, J. M., and Herzing, L. B., Expression cloning of multiple human cDNAs that complement the phenotypic defects of ataxia-telangiectasia group D fibroblasts. Am. J. hum. Genet.53 (1993) 1206–1216.

    PubMed  Google Scholar 

  104. Murnane, J. P., and Painter, R. B., Complementation of the defects in DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells. Proc. natl Acad. Sci. USA79 (1982) 1960–1963.

    PubMed  Google Scholar 

  105. Murnane, J. P., and Kapp, L. N., A critical look at the association of human genetic syndromes with sensitivity to ionizing radiation. Sem. Cancer Biol.4 (1993) 93–104.

    Google Scholar 

  106. Murray, A. W., Creative blocks; cell cycle checkpoints and feedback controls. Nature, Lond.359 (1992) 599–604.

    Google Scholar 

  107. Muschel, R. J., Zhang, H. B., Hiakis, G., and McKenna, W. G., Cyclin B expression in HeLa cells during the G2 block induced by ionizing radiation. Cancer Res.51 (1991) 5113–5117.

    PubMed  Google Scholar 

  108. Muschel, R. J., Zhang, H. B., and McKenna, W. G., Differential effect of ionizing radiation on the expression of cyclin A and cyclin B in HeLa cells. Cancer Res.53 (1993) 1128–1135.

    PubMed  Google Scholar 

  109. Nagasawa, H., and Little, J. B., Comparison of kinetics of X-ray-induced cell killing in normal, ataxia-telangiectasia and hereditary retinoblastoma fibroblasts. Mutat. Res.109 (1983) 297–308.

    PubMed  Google Scholar 

  110. Nagasawa, H., Latt, S. A., Lalande, M. E., and Little, J. B., Effects of X-irradiation on cell-cycle progression, induction of chromosomal aberrations and cell killing in ataxia-telangiectasia (AT) fibroblasts. Mutat. Res.148 (1985) 71–82.

    PubMed  Google Scholar 

  111. Nasrin, N., Kunhi, M., Einspenner, M., Al Sedairy, A., and Hannan, M., Reduced induction of p53 protein by gamma-irradiation in ataxia telangiectasia cells without constitutional mutations in exons 5, 6, 7 and 8 of the p53 gene. Cancer Genet. Cytogenet.77 (1994) 14–18.

    PubMed  Google Scholar 

  112. North, P., Ganesh, A., and Thacker, J., The rejoining of double-strand breaks in DNA by human cell extracts. Nucl. Acids Res.18 (1990) 6205–6210.

    PubMed  Google Scholar 

  113. Nurse, P., Universal control mechanism regulating onset of M-phase. Nature, Lond.344 (1990) 503–508.

    Google Scholar 

  114. Nurse, P., Ordering S phase and M phase in the cell cycle. Cell79 (1994) 547–550.

    PubMed  Google Scholar 

  115. O'Connor, P. M., Jackman, J., Jondle, D., Bhatia, K., Margrath, I., and Kohn, K. W., Role of the p53 tumour suppressor gene in cell cycle arrest and radiosensitivity of Burkitt's lymphoma cell lines. Cancer Res.53 (1993) 4776–4780.

    PubMed  Google Scholar 

  116. Painter, R. B., and Robertson, J. S., Effect of irradiation and theory of role of mitotic delay on the time course of labeling of HeLa S3 cells with tritiated thymidine. Radiat. Res.11 (1959) 206–217.

    PubMed  Google Scholar 

  117. Painter, R. B., The direct effect of X-irradiation on HeLa S3 deoxyribonucleic acid synthesis. Radiat. Res.16 (1962) 846–859.

    PubMed  Google Scholar 

  118. Painter, R. B., Radioresistant DNA synthesis: an intrinsic feature of ataxia-telangiectasia. Mutat. Res.84 (1981) 183–190.

    PubMed  Google Scholar 

  119. Painter, R. B., and Young, B. R., X-ray-induced inhibition of DNA synthesis in Chinese hamster ovary, human HeLa and mouse L cells. Radiat. Res.64 (1975) 648–656.

    PubMed  Google Scholar 

  120. Painter, R. B., and Young, B. R., Formation of nascent DNA molecules during inhibition of replicon initiation in mammalian cells. Biochim. biophys. Acta.418 (1976) 146–153.

    PubMed  Google Scholar 

  121. Painter, R. B., and Young, B. R., Radiosensitivity in ataxiatelangicetasia: a new explanation. Proc. natl Acad. Sci. USA77 (1980) 7315–7317.

    PubMed  Google Scholar 

  122. Pandita, T. K., and Hittelman, W. N., Initial chromosome damage but not DNA damage is greater in ataxia telangiectasia cells. Radiat Res.130 (1992) 94–103.

    PubMed  Google Scholar 

  123. Pandita, T. K., and Hittelman, W. N., Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cells. Mutat. Research310 (1994) 1–13.

    Google Scholar 

  124. Pandita, T. K., and Hittelman, W. N., The constribution of DNA and chromosome repair deficiencies to the radiosensitiveity of ataxia-telangiectasia. Radiat. Res.131 (1995) 214–223.

    Google Scholar 

  125. Papathanasiou, M. A., Kerr, N. C., Robbins, J. H., McBride, O. W., Alamo, I. Jr., Barrett, S. F., Hickson, I. D., and Fornace, A. J. Jr., Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C. Molec. cell. Biol.11 (1991) 1009–1016.

    PubMed  Google Scholar 

  126. Perry, M. E., Piette, J., Zanwadziki, J. A., Harvey, D., and Levine, A. J., The mdm-2 gene is induced in response to UV-light in a p53-dependent manner. Proc. natl Acad. Sci. USA90 (1993) 11623–11627.

    PubMed  Google Scholar 

  127. Powell, S., Whitaker, S., Peacock, J., and McMillan, T., Ataxia-telangiectasia: An investigation of the repair defect in the cell line AT5BIVA by plasmid reconsitution. Mutat. Res.294 (1993) 9–20.

    PubMed  Google Scholar 

  128. Prelich, G., Kostura, M., Marshak, D. R., Mathews, M. B., and Stillman, B., The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. Nature, Lond.326 (1987) 471–475.

    Google Scholar 

  129. Price, B. D., and Park, S. J., DNA damage increases the levels of MDM2 messenger RNA in wtp53 human cells. Cancer Res.54 (1994) 896–899.

    PubMed  Google Scholar 

  130. Rasmussen, R. E., and Painter, R. B., Radiation stimulated DNA synthesis in cultured mammalian cells. J. Cell Biol.29 (1966) 11–19.

    PubMed  Google Scholar 

  131. Rayeroft, L., Wu, H. Y., and Lozano, G., Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science249 (1990) 1049–1051.

    PubMed  Google Scholar 

  132. Rotman, G., Savitski, K., Vanagaite, L., Bar-Shira, A., Ziv, Y., Gilad, S., Uchenik, V., Smith, S., and Shiloh, Y., Physical and genetic mapping at the ATA/ATC locus in chromosome 11q22–23. Int. J. Radiat. Biol.66 (1994) S63-S66.

    PubMed  Google Scholar 

  133. Rudolph, N. S., and Latt, S. A., Flow cytometric analysis of X-ray sensitivity in ataxia-telangiectasia. Mutat. Res.211 (1989) 31–41.

    PubMed  Google Scholar 

  134. Runger, T. M., Poot, M., and Kraemer, K. H., Abnormal processing of transfected plasmid DNA in cells from patients with ataxia telangiectasia. Mutat. Res.293 (1993) 47–54.

    Google Scholar 

  135. Sanal, O., Lange, E., Telatar, M., Sobel, E., Salazar-Novak, J., Ersoy, F., Morrison, A., Concannon, P., Tolun, A., and Gatti, R. A., Ataxia telangiectasia: linkage analysis of chromosome 11q22–23 markers in Turkish families. FASEB J.6 (1992) 2848–2852.

    PubMed  Google Scholar 

  136. Santhanam, U., Ray, A., and Sehgal, P. B., Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product. Proc. natl Acad. Sci. USA88 (1991) 7605–7609.

    PubMed  Google Scholar 

  137. Sasaki, M. S., and Taylor, A. M. R., Dissociation between radioresistant DNA replication and chromosomal radiosensitivity in ataxia telangiectasia cells. Mutat. Research307 (1994) 107–113.

    Google Scholar 

  138. Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., Ashkenazi, M., Pecker, I., Frydman, M., Harnik, R., Patanjali S. R., Simmons, A., Clines, G. A., Sartiel, A., Gatti, R. A., Chessa, L., Sanal, O., Lavin, M. F., Jaspers, N. G. J., Taylor, A. M. R., Arlett, C. F., Miki, T., Weissman, S. M., Lovett, M., Collins, F. S. and Shiloh, Y., A single Ataxia telangiectasia gene with a product similar to PI-3 kinase. Science268 (1995) 1749–1753.

    PubMed  Google Scholar 

  139. Scaife, J. F., Mitotic G2 delay induced in synchronized human kidney cells by UV and x-irradiation and its relation to DNA strand breakage, repair and transcription. Cell Tissue Kinet.3 (1970) 229–242.

    PubMed  Google Scholar 

  140. Schneider, D. O., and Johns, R. M., Enhancement of radiation induced mitotic inhibition by BUdR incorporation in L-cells. Radiat. Res.28 (1966) 657–667.

    PubMed  Google Scholar 

  141. Scott, D., Spreadborough, A. R., and Roberts, S. A., Radiation-induced G2 delay and spontaneous chromosome aberrations in ataxia-telangiectasia homozygotes and heterozygotes. Int. J. Radiat. Biol.66 (1994) S157-S163.

    PubMed  Google Scholar 

  142. Shen, Y., and Shenk, T., Relief of p53-mediated transcriptional repression by the adenovirus E1B 19kDa protein or the cellular Bcl-2 protein. Proc. natl Acad. Sci. USA91 (1994) 8940–8944.

    PubMed  Google Scholar 

  143. Sherr, C. J., G1 phase progression: cycling on cue. Cell79 (1994) 551–555.

    PubMed  Google Scholar 

  144. Shirodkar, S., Ewen, M., DeCaprio, J. A., Morgan, J., Livingston, D. M., and Chittenden, T., The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin-A complex in a cell cycle-regulated manner. Cell68 (1992) 157–166.

    PubMed  Google Scholar 

  145. Shivji, K. K., Kenny, M. K., and Wood, R. D., Proliferating cell nuclear antigen is required for DNA excision repair. Cell69 (1992) 367–374.

    PubMed  Google Scholar 

  146. Shung, B., Miyakoshi, J., and Takebe, H., X-ray-induced transcriptional activation of c-myc and XRCC1 genes in ataxia telangiectasia cells. Mutat. Res.307 (1994) 43–51.

    PubMed  Google Scholar 

  147. Sinclair, W. K., Cyclic x-ray responses in mammalian cells in vitro. Radiat. Biol.33 (1968) 620–643.

    Google Scholar 

  148. Singh, S. P., and Lavin, M. F., DNA-binding protein activated by gamma radiation in human cells. Molec. cell. Biol.10 (1990) 5279–5285.

    PubMed  Google Scholar 

  149. Slichenmyer, W. J., Nelson, W. G., Slebos, R. J., and Kastan, M. B., Loss of p53 associated G1 checkpoint does not decrease cell survival following DNA damage. Cancer Res.53 (1993) 4164–4168.

    PubMed  Google Scholar 

  150. Smets, L. A., On the increased precursor incorporation into DNA of irradiated mammalian cells. Int. J. Radiat. Biol.14 (1968) 585–588.

    Google Scholar 

  151. Smith, P. J., Anderson, C. O., and Watson, J. V., Abnormal retention of X-irradiated ataxia-telangiectasia fibroblasts in G2 phase of the cell cycle: cellular RNA content, chromatin stability and the effects of 3-aminobenzamide. Int. J. Radiat. Biol.47 (1985) 701–712.

    Google Scholar 

  152. Stein, B., Baldwin, A. S. Jr., Ballard, D. W., Greene, W. C., Angel, P., and Herrlich, P., Cross-coupling of the NF-kB p65 and Fos/Jun transcription factors produces potentiated biological function. EMBO J.12 (1993) 3879–3891.

    PubMed  Google Scholar 

  153. Strickler, J. G., Zheng, J., Shu, Q., Burgart, L. J., Alberts, S. R., and Shibata, D., p53 mutations and microsatellite instability in sporadic gastric cancer: when guardians fail. Cancer Res.54 (1994) 4750–4755.

    PubMed  Google Scholar 

  154. Sukhatme, V. P., Early transcriptional events and cell growth: the Egr-1 family. Am. Soc. Nephrol.1 (1990) 859–866.

    Google Scholar 

  155. Taccioli, G., Rathbun, G., Oltz, E., Stamato, T., Jeggo, P., and Alt, F., Impairment, of V(D) J recombination in doublestrand break repair mutants. Science260 (1993) 207–210.

    PubMed  Google Scholar 

  156. Taccioli, G. E., Gottlieb, T. M., Blunt, T., Priestley, A., Demengeot, J., Mizuta, R., Lehmann, A. R., Alt, F. W., Jackson, S. P., and Jeggo, P. A., Ku80: Product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science265 (1994) 1442–1445.

    PubMed  Google Scholar 

  157. Tatsumi-Miyajima, J., Yagi, T., and Takebe, H., Analysis of mutations caused by DNA double-strand breaks produced by a restriction enzyme in shuttle vector plasmids propagated in ataxia-telangiectasia cells. Mutat. Res.294 (1993) 317–323.

    PubMed  Google Scholar 

  158. Taya, Y., Yasuda, H., Kamijo, M., Nakaga, K., Nakamura, Y., Ohba, Y., and Nishimura, S., In vitro phosphorylation of the tumor suppressor gene RB protein by mitosis-specific histone H1 kinase. Biochem. biophys. Res. Comm.164 (1989) 580–586.

    PubMed  Google Scholar 

  159. Taylor, A. M., Harnden, D. G., Arlett, C. F., Harcourt, S. A., Lehmann, A. R., Stevens, S., and Bridges, B. A., Ataxiatelangiectasia: a human mutation with abnormal radiation sensitivity. Nature, Lond.258 (1975) 427–429.

    Google Scholar 

  160. Teale, B., Khanna, K. K., Singh, S. P., and Lavin, M. F., Radiation-activated DNA-binding protein constitutively present in ataxia telangiectasia nuclei. J. biol. Chem.268 (1993) 22450–22455.

    PubMed  Google Scholar 

  161. Terasima, Y., and Tolmach, L. J., Variations in several responses of HeLa cells to X-irradiation during the division cycle. Biophys. J.3 (1963) 11–33.

    PubMed  Google Scholar 

  162. Thacker, J., and Wilkinson, R. E., The genetic basis of resistance to ionizing radiation damage in cultured mammalian cells. Mutat. Res.254 (1991) 135–142.

    PubMed  Google Scholar 

  163. Thacker, J., Chalk, J., Ganesh, A., and North, P., A mechanism for deletion formation in DNA by human cell extracts: the involvement of short sequence repeats. Nucl. Acids Res.20 (1992) 6183–6188.

    PubMed  Google Scholar 

  164. Thacker, J., Cellular radiosensitivity in ataxia-telangiectasia. Int. J. Radiat. Biol.66 (1994) 587–596.

    Google Scholar 

  165. Thompson, L. H., Brookman, K. W., Jones, N. J., Allen, S. A., and Carrano, A. V., Molecular cloning of the human XRCC1 gene, which corrects defective DNA strandbreak repair and sister chromatid exchange. Molec. cell. Biol.10 (1990) 6160–6171.

    PubMed  Google Scholar 

  166. Todorov, I. T., Pepperkok, R., Philipova, R. N., Kearsey, S. E., Ansorge, W., and Werner, D., a human nuclear proein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division. J. cell. Sci.107 (1994) 253–265.

    PubMed  Google Scholar 

  167. Tolmach, L. J., Jones, R. W., and Busse, P. M., The action of caffeine on X-irradiated HeLa cells. I Delayed inhibition of DNA synthesis. Radiat. Res.71 (1977) 653–665.

    PubMed  Google Scholar 

  168. Walters, R. A., and Petersen, D. F., Radiosensitivity of mammalian cells I. Timing and dose-dependence of radiation induced division delay. Biophys. J.8 (1968) 1475–1486.

    PubMed  Google Scholar 

  169. Walters, R. A., and Hildebrand, C. E., Evidence that x-irradiation inhibits DNA replicon initiation in Chinese hamster cells. Biochem. biophys. Res. Comm.,65 (1975) 265–271.

    PubMed  Google Scholar 

  170. Wang, Y., and Iliakis, G., Prolonged inhibition by X-rays of DNA synthesis in cells obtained by transformation of primary rat embryo fibroblasts with oncogenes H-ras and vmyc. Cancer Res.52 (1992) 508–514.

    PubMed  Google Scholar 

  171. Wang, Y., Cheong, N., and Iliakis, G., Persistant inhibition of DNA synthesis in irradiated rat embryo fibroblasts expressing the oncogenes H-ras plus v-myc derives from inhibition of replicon initiation and is mitigated by staurosporine. Cancer Res.53 (1993) 1213–1217.

    PubMed  Google Scholar 

  172. Warters, R. L., Radiation-induced apoptosis in a murine T-cell hybridoma. Cancer Res.52 (1992) 883–890.

    PubMed  Google Scholar 

  173. Watanabe, I., Radiation effects on DNA chain growth in mammalian cells. Radiat. Res.58 (1974) 541–556.

    PubMed  Google Scholar 

  174. Watt, P. M., and Hickson, I. D., Structure and function of type II DNA topoisomerases. Biochem. J.303 (1994) 681–695.

    PubMed  Google Scholar 

  175. Weichselbaum, R. R., Hallahan, D. E., Sukhatme, V., Dritschilo, A., Sherman, M. L., and Kufe, D. W., Biological consequences of gene regulation after ionizing radiation exposure. J. Natl. Cancer Inst.83 (1991) 480–484.

    PubMed  Google Scholar 

  176. Weichselbaum, R. R., Hallahan, D., Fuks, Z., and Kufe, D., Radiation induction of immediate early genes: effectors of the radiation-stress responses. Int. J. radiat. Onc. biol. Phys.30 (1994) 229–234.

    Google Scholar 

  177. Weinert, T., and Lydall, D., Cell cycle checkpoints, genetic instability and cancer. Cancer Biol.4 (1993) 129–140.

    Google Scholar 

  178. Wold, M. S., Weinberg, D. H., Virshup, D. M., Li, J. J., and Kelly, T. J., Identification of cellular proteins required for simian virus 40 DNA replication. J. biol. Chem.264 (1989) 2801–2809.

    PubMed  Google Scholar 

  179. Wu, Y., Liu, Y., Lee, L., Miner, Z., and Kules-Martin, M., Wild-type alternatively spliced p53: binding to DNA and interaction with the major p53 protein in vitro and in cells. EMBO J.13 (1994) 4823–4830.

    PubMed  Google Scholar 

  180. Wyllie, A. H., Cell death: the significance of apoptosis. Int. Rev. Cytol.68 (1980) 251–306.

    PubMed  Google Scholar 

  181. Xiong, Y., Hannon, G. J., Zhang, H., Casso, D., Kobayashi, R., and Beach, D., p21 is a universal inhibitor of cyclin kinases. Nature, Lond.366 (1993) 701–704.

    Google Scholar 

  182. Yamada, M., and Puck, T. T., Action of radiation on mammalian cells, IV. Reversible mitotic lag in the S3 HeLa cell produced by low doses of X-rays. Proc. natl Acad. Sci. USA47 (1961) 1181–1191.

    PubMed  Google Scholar 

  183. Young, B. R., and Painter, R. B., Radioresistant DNA synthesis and human genetic diseases. Hum. Genet.82 (1989) 113–117.

    PubMed  Google Scholar 

  184. Zampetti-Bosseler, F., and Scott, D., Cell death, chromosome damage and mitotic delay in normal human, ataxia-telangiectasia and retinoblastoma fibroblasts after X-irradiation. Int. J. Radiat. Biol.39 (1981) 547–558.

    Google Scholar 

  185. Zdzienicka, M. Z., van Wessel, N., and van der Schans G. P., A fourth complementation group among ionising radiation-sensitive Chinese hamster cell mutants defective in DNA double-strand break repair. Radiat. Res.131 (1992) 309–314.

    PubMed  Google Scholar 

  186. Zuber, M., Tan, E. M., and Ryoji, M., Involvement of proliferating cell nuclear antigen (cyclin) in DNA replication in living cells. Molec. cell. Biol.9 (1989) 57–66.

    PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Gray Laboratory, Mount Vernon Hospital, HA6 2JR, Northwood, UK

    H. D. Lohrer

Authors
  1. H. D. Lohrer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lohrer, H.D. Regulation of the cell cycle following DNA damage in normal and Ataxia telangiectasia cells. Experientia 52, 316–328 (1996). https://doi.org/10.1007/BF01919534

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01919534

Key words

  • Ataxia telangiectasia
  • cell cycle
  • radiation resistant DNA synthesis
  • DNA damage
  • DNA repair
  • cell cycle check point