Metaphase fragility of the human RNU1 and RNU2 loci is induced by actinomycin D through a p53-dependent pathway

Human Molecular Genetics

Volumn 7, Issue 4, 1998, Pages 609-617

  Yu, Adong ^a   Bailey, Arnold D ^a   Weiner, Alan M ^a,b  

^a YALE UNIVERSITY   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APHIDICOLIN; CYTARABINE; DACTINOMYCIN; PROTEIN P53; SMALL NUCLEAR RNA;

ADENOVIRUS 12; ANIMAL CELL; ARTICLE; CHROMOSOME FRAGILITY; CONTROLLED STUDY; METAPHASE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; RNA GENE; VIRUS INFECTION;

CHROMOSOME FRAGILITY; DACTINOMYCIN; GENES, P53; HUMANS; IN SITU HYBRIDIZATION, FLUORESCENCE; METAPHASE; NUCLEIC ACID SYNTHESIS INHIBITORS; RNA, SMALL NUCLEAR; TUMOR CELLS, CULTURED;

ADENOVIRIDAE; ANIMALIA; HUMAN ADENOVIRUS TYPE 12; RNA VIRUSES;

EID: 0031896599     PISSN: 09646906     EISSN: None     Source Type: Journal    
DOI: 10.1093/hmg/7.4.609     Document Type: Article

References (100)

1. Miro, R., Clemente, I.C., Fuster, C. and Egozcue, J. (1987) Fragile sites, chromosome evolution, and human neoplasia. Hum. Genet., 75, 345-349.
2. Popescu, N.C., Zimonjic, D. and DiPaolo, J.A. (1990) Viral integration, fragile sites, and proto-oncogenes in human neoplasia. Hum. Genet., 84, 383-386.
3. Wilke, C.M., Hall, B.K., Hoge, A., Pardee, W., Smith, D.I. and Glover, T.W. (1996) FRAA3B extends over a broad region and contains a spontaneous HPV integration site: direct evidence for the coincidence of viral integration sites and fragiles sites. Hum. Mol. Genet., 5, 187-195.
4. Rassool, F.V., McKeithan, T.W., Neilly, M.E., van Melle, E., Espinosa, R.D. and Le Beau, M.M. (1991) Preferential integration of marker DNA into the chromosomal fragile site at 3p14: an approach to cloning fragile sites. Proc. Natl Acad. Sci. USA, 88, 6657-6661.
5. Coquelle, A., Pipiras, E., Toledo, F., Buttin, G. and Debatisse, M. (1997) Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to early amplicons. Cell, 89, 215-225.
6. Glover, T.W. and Stein, C.K. (1987) Induction of sister chromatid exchanges at common fragile sites. Am. J. Hum. Genet., 41, 882-890.
7. Gaddini, L., Pelliccia, F., Limongi, M.Z. and Rocchi, A. (1995) Study of the relationships between common fragile sites, chromosome breakages and sister chromatid exchanges. Mutagenesis, 10, 257-260.
8. Wenger, S.L. (1995) Chemical induction of sister chromatid exchange at fragile sites. Cancer Genet. Cytogenet., 85, 72-74.
9. zur Hausen, H. (1967) Induction of specific chromosomal aberrations by adenovirus type 12 in human embryonic kidney cells. J. Virol., 1, 1174-1185.
10. Schramayr, S., Caporossi, D., Mak, I., Jelinek, T. and Bacchetti, S. (1990) Chromosomal damage induced by human adenovirus type 12 requires expression of the ElB 55 kilodalton viral protein. J Virol., 64, 2090-2095.
11. Bernstein, L.B., Manser, T. and Weiner, A.M. (1985) Human U1 small nuclear RNA genes: evidence for extensive conservation of flanking sequences suggests cycles of gene amplification and transposition. Mol. Cell. Biol., 5, 2159-2171.
12. Lindgren, V., Ares, M., Weiner, A.M. and Francke, U. (1985) Human genes for U2 small nuclear RNA map to a major adenovirus 12 modification site on chromosome 17. Nature, 314, 115-116.
13. Lindgren, V.L., Bernstein, L.B., Weiner, A.M. and Francke, U. (1985) Human U1 small nuclear RNA pseudogenes do not map to the site of the U1 genes in 1p36 but are clustered in 1q12-q22. Mol. Cell. Biol., 5, 2172-2180.
14. Sorensen, P.D., Lomholt, B., Frederiksen, S. and Tommerup, N. (1991) Fine mapping of human 5S rRNA genes to chromosome 1q42.11-q42.13. Cytogenit. Cell Genet., 57, 26-29.
15. Dumam, D.M., Menninger, J.C., Chandler, S.H., Smith, P.P. and McDougall, J.K. (1988) A fragile site in the human U2 small nuclear RNA gene cluster is revealed by adenovirus type 12 infection. Mol Cell. Biol., 8, 1863-1867.
16. Li, Y.P., Tomanin, R., Smiley, J.R. and Bacchetti, S. (1993) Generation of a new adenovirus type 12-inducible fragile site by insertion of an artificial U2 locus in the human genome. Mol. Cell. Biol., 13, 6064-6070.
17. Bailey, A.D., Li, Z., Pavelitz, T. and Weiner, A.M. (1995) Adenovirus 12-induced fragility of the human RNU2 locus requires U2 snRNA transcriptional regulatory elements. Mol. Cell. Biol., 15, 6246-6255.
18. Gargano, S., Wang, P., Rusanganwa, E. and Bacchetti, S. (1995) The transcriptionally competent U2 gene is necessary and sufficient for adenovirus type 12 induction of the fragile site at 17q21-22. Mol. Cell. Biol., 15, 6256-6261.
19. Pavelitz, T., Rusché, L., Matera, A.G., Scharf, J.M. and Weiner, A.M. (1995) Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus. EMBO J., 14, 169-177.
20. Liao, D., Pavelitz, T., Kidd, J., Kidd, K. and Weiner, A.M. (1997) Concerted evolution of the tandemly repeated genes encoding human U2 snRNA (the RNU2 locus) involves rapid intrachromosomal homogenization and rare interchromosomal gene conversion. EMBO J., 16, 588-598.
21. n microsatellite embedded within the U2 repeat unit. Genomics, 30, 583-593.
22. Liao, D., Pavelitz, T. and Weiner, A.M. (1998) Characterization of a novel class of interspersed LTR elements in primate genomes: structure, genomic distribution, and evolution. J. Mol. Evol., 41, in press.
23. Shenk, T. (1996) Adenoviridae: the viruses and their replication. In Fields, B.N. (ed.), Virology. Lippincott-Raven, Philadelphia, PA, pp. 2111-2148.
24. Durnam, D.M., Smith, P.P., Menninger, J.C. and McDougall, J.K. (1986)The E1 region of human adenovirus type 12 determines the sites of virally induced chromosomal damage. In Botchan, M. et al. (eds), Cancer Cells 4: DNA Tumor Viruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 349-354.
25. Kao, C.C., Yew, P.R. and Berk, A.J. (1990) Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. Virology, 179, 806-814.
26. Yew, P.R., Liu, X. and Berk, A.J. (1994) Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev., 8, 190-202.
27. Bischoff, J.R., Kim, D.H., Williams, A., Heise, C., Horn, S., Muna, M., Ng, L., Nye, J.A., Sampson-Johannes, A., Fattacy, A. and McCormick, F. (1996) An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science, 274, 373-376.
28. Dobner, T., Horikoshi, N., Rubenwolf, S. and Shenk, T. (1996) Blockage by adenovirus E4orf6 of transcriptional activation by the p53 tumor suppressor. Science, 272, 1470-1473.
29. Nevels, M., Rubenwolf, S., Spruss, T., Wolf, H. and Dobner, T. (1997) The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function. Proc. Natl Acad. Sci. USA, 94, 1206-1211.
30. Goodrum, F.D., Shenk, T. and Ornelles, D.A. (1996) Adenovirus early region 4 34-kilodalton protein directs the nuclear localization of the early region 1B 55-kilodalton protein in primate cells. J. Virol., 70, 6323-6335.
31. Li, Z., Yu, A. and Weiner, A.M. (1998) Adenovirus 12-induced fragility of the human RNU2 locus requires p53 function. J. Virol., 72, in press.
32. Kastan, M.B., Onyekwere, O., Sidransky, D., Vogelstein, B. and Craig, R.W. (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res., 51, 6304-6311.
33. Tishler, R.B., Calderwood, S.K., Coleman, C.N. and Price, B.D. (1993) Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents. Cancer Res., 53, 2212-2216.
34. Bates, S., Rowan, S. and Vousden, K.H. (1996) Characterization of human cyclin G1 and G2: DNA damage inducible genes. Oncogene, 13, 1103-1109.
35. Price, B.D. and Youmell, M.B. (1996) The phosphatidylinositol 3-kinase inhibitor wortmannin sensitizes murine fibroblasts and human tumor cells to radiation and blocks induction of p53 following DNA damage. Cancer Res., 56, 246-250.
36. Uzvolgyi, E., Classon, M., Henriksson, M., Huang, M., Szekely, L., Lee, W.H., Klein, G. and Sumegi, J. (1991) Reintroduction of a normal retinoblastoma gene into retinoblastoma and osteosarcoma cells inhibits the replication associated function of SV40 large T antigen. Cell Growth Differ., 2, 297-303.
37. Zhang, W., Funk, W.D., Wright, W.E., Shay, J.W. and Deisseroth, A.B. (1993) Novel DNA binding of p53 mutants and their role in transcriptional activation. Oncogene, 8, 2555-2559.
38. Ory, K., Legros, Y., Auguin, C. and Soussi, T. (1994) Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation. EMBO J., 13, 3496-3504.
39. Wang, X.W., Vermeulen, W., Coursen, J.D., Gibson, M., Lupold, S.E., Forrester, K., Xu, G., Elmore, L., Yeh, H., Hoeijmakers, J.H. and Harris, C.C. (1996) The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. Genes Dev., 10, 1219-1232.
40. Steegenga, W.T., van Laar, T., Riteco, N., Mandarino, A., Shvarts, A., van der Eb, A.J. and Jochemsen, A.G. (1996) Adenovirus E1A proteins inhibit activation of transcription by p53. Mol. Cell. Biol., 16, 2101-2109.
41. Horikoshi, N., Usheva, A., Chen, J., Levine, A.J., Weinmann, R. and Shenk, T. (1995) Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression. Mol. Cell. Biol., 15, 227-234.
42. Haaf, T. and Ward, D.C. (1996) Inhibition of RNA polymerase II transcription causes chromatin decondensation, loss of nucleolar structure, and dispersion of chromosomal domains. Exp. Cell Res., 224, 163-173.
43. Kessler, O., Jiang, Y. and Chasin, L.A. (1993) Order of intron removal during splicing of endogenous adenine phosphoribosyltransferase and dihydrofolate reductase pre-mRNA. Mol. Cell. Biol., 13, 6211-6222.
44. Hemandez, N. (1985) Formation of the 3′ end of U1 snRNA is directed by a conserved sequence located downstream of the coding region. EMBO J., 4, 1827-1837.
45. Yuo, C.-Y., Ares, M. and Weiner, A.M. (1985) Sequences required for 3′ end formation of human small nuclear RNA U2. Cell, 42, 193-202.
46. Jacobson, M.R., Rhoadhouse, M. and Pederson, T. (1993) U2 small nuclear RNA 3′ end formation is directed by a critical internal structure distinct from the processing site. Mol. Cell. Biol., 13, 1119-1129.
47. Kastan, M.B., Zhan, Q., El-Deiry, W.S., Carrier, F., Jacks, T., Walsh, W., Plunkett, B.S., Vogelstein, B. and Fornace, A J. (1992) A mammalian cell cycle checkpoint utilizing p53 and gadd45 is defective in ataxia telangiectasia. Cell, 71, 587-597.
48. Nelson, W.G. and Kastan, M.B. (1994) DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways. Mol. Cell. Biol., 14, 1815-1823.
49. Jongmans, W., Artuso, M., Vuillaume, M., Bresil, H., Jackson, S.P. and Hall, J. (1996) The role of ataxia telangiectasia and the DNA-dependent protein kinase in the p53-mediated cellular response to ionising radiation. Oncogene, 13, 1133-1138.
50. Rathmell, W.K., Kaufmann, W.K., Hurt, J.C., Byrd, L.L. and Chu, G. (1997) DNA-dependent protein kinase is not required for accumulation of p53 or cell cycle arrest after DNA damage. Cancer Res., 57, 68-74.
51. Pritsche, M., Haessler, C. and Brandner, G. (1993) Induction of nuclear accumulation of the tumor-suppresor protein p53 by DNA-damaging agents. Oncogene, 8, 307-318.
52. Trask, D.K. and Muller, M.T. (1988) Stabilization of type I topoisomerase-DNA covalent complexes by actinomycin D. Proc. Natl Acad. Sci. USA, 85, 1417-1421.
53. Wassermann, K., Markovits, J., Jaxel, C., Capranico, G., Kohn, K.W. and Pommier, Y. (1990) Effects of morpholinyl doxorubicins, doxorubicin, and actinomycin D on mammalian topoisomerases I and II. Mol. Pharmacol., 38, 38-45.
54. Piret, B. and Piette, J. (1996) Topoisomerase poisons activate the transcription factor NF-kappaB in ACH-2 and CEM cells. Nucleic Acids Res., 24, 4242-4248.
55. Hoekstra, M.F. (1997) Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family. Curr. Opin. Genet. Dev., 7, 170-175.
56. Khanna, K.K., Beamish, H., Yan, J., Hobson, K., Williams, R., Dunn, I. and Lavin, M.F. (1995) Nature of the G1-S cell cycle checkpoint defect in ataxia-telangiectasia. Oncogene, 11, 609-618.
57. Fried, L.M., Koumenis, C., Peterson, S.R., Green, S.L., van Zijl, P., Allalunis-Tumer, J., Chen, D.J., Fishel, R., Giaccia, A.J., Brown, J.M. and Kirchgessner, C.U. (1996) The DNA damage response in DNA-dependent protein kinase-deficient SCID mouse cells: replication protein A hyperphos-phorylation and p53 induction. Proc. Natl Acad. Sci. USA, 93, 13825-13830.
58. Cary, R.B., Peterson, S.R., Wang, J., Bear, D.G, Bradbury, E.M. and Chen, D.J. (1997) DNA looping by Ku and the DNA-dependent protein kinase. Proc. Natl Acad. Sci. USA, 94, 4267-4272.
59. Anderson, C.W. (1993) DNA damage and the DNA-activated protein kinase. Trends Biochem. Sci., 18, 433-437.
60. MacArthur, H.L., Agarwal, M.L. and Bacchetti, S. (1998) Induction of fragility at the human RNU2 locus by cytosine arabinoside is dependent upon a transcriptionally competent U2 small nuclear RNA gene and the expression of p53. Som. Cell Mol. Genet., 23, in press.
61. Hedley, D.W. and McCulloch, E.A. (1996) Generation of reactive oxygen intermediates after treatment of blasts of acute myeloblastic leukemia with cytosine arabinoside: role of bcl-2. Leukemia, 10, 1143-1149.
62. Leresche, A., Wolf, V.J. and Gottesfeld, J.M. (1996) Repression of RNA polymerase II and III transcription during M phase of the cell cycle. Exp. Cell Res., 229, 282-288.
63. Segil, N., Guermah, M., Hoffmann, A., Roeder, R.G. and Heintz, N. (1996) Mitotic regulation of TFIID: inhibition of activator-dependent transcription and changes in subcellular localization. Genes Dev., 10, 2389-2400.
64. Segil, N., Roberts, S.B. and Heintz, N. (1991) Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity. Science, 254, 1814-1816.
65. Martinez-Balbas, M.A., Dey, A., Rabindran, S.K., Ozato, K. and Wu, C. (1995) Displacement of sequence-specific transcription factors from mitotic chromatin. Cell, 83, 29-38.
66. Gottesfeld, J.M., Wolf, V.J., Dang,T., Forbes, D.J. and Hartl, P. (1994) Mitotic repression of RNA polymerase III transcription in vitro mediated by phosphorylation of a TFIIIB component. Science, 263, 81-84.
67. White, R.J., Gottlieb, T.M., Downes, C.S. and Jackson, S.P. (1995) Mitotic regulation of a TATA-binding-protein-containing complex. Mol. Cell. Biol., 15, 1983-1992.
68. Stukenberg, P.T., Lustig, K.D., McGarry, T.J., King, R.W., Kuang, J. and Kirschner, M.W. (1997) Systematic identification of mitotic phosphoproteins. Cuir. Biol, 7, 338-348.
69. Shermoen, A.W. and O'Farrell, P. H. (1991) Progression of the cell cycle through mitosis leads to abortion of nascent transcripts. Cell, 67, 303-310.
70. Michelotti, E.F., Sanford, S. and Levens, D. (1997) Marking of active genes on mitotic chromosomes. Nature, 388, 895-899.
71. Henry, R.W., Ma, B., Sadowski, C.L., Kobayashi, R. and Hernandez, N. (1996) Cloning and characterization of SNAP50, a subunit of the snRNA-activating protein complex SNAPc. EMBO J., 15, 7129-7136.
72. Bai, L., Wang, Z., Yoon, J.B. and Roeder, R.G. (1996) Cloning and characterization of the beta subunit of human proximal sequence element-binding transcription factor and its involvement in transcription of small nuclear RNA genes by RNA polymerases II and III. Mol. Cell. Biol., 16, 5419-5426.
73. Sadowski, C.L., Henry, R.W., Kobayashi, R. and Hernandez, N. (1996) The SNAP45 subunit of the small nuclear RNA (snRNA) activating protein complex is required for RNA polymerase II and III snRNA gene transcription and interacts with the TATA box binding protein. Proc. Natl Acad. Sci. USA, 93, 4289-4293.
74. Hernandez, N. and Weiner, A.M. (1986) Formation of the 3′ end of U1 snRNA requires compatible snRNA promoter elements. Cell, 47, 249-258.
75. Neuman de Vegvar, H.E., Lund, E. and Dahlberg, J.E. (1986) 3′ end formation of U1 snRNA precursors is coupled to transcription from snRNA promoters. Cell, 47, 259-266.
76. Hernandez, N. and Lucito, R. (1988) Elements required for transcription initiation of the human U2 snRNA gene coincide with elements required for snRNA 3′ end formation. EMBO J., 7, 3125-3134.
77. Eliceiri, G.L. (1976) Some properties of the small homodisperse RNAs in the cytoplasm of HeLa cells. Biochim. Biophys. Acta, 425, 202-207.
78. Eliceiri, G.L. (1979) Sensitivity of low molecular weight RNA synthesis to UV radiation. Nature, 279, 80-81.
79. Morra, D.S., Eliceiri, B.P. and Eliceiri, G.L. (1986) Effect of UV light on small nuclear RNA synthesis: increased inhibition during postirradiation cell incubation. Mol. Cell. Biol., 6, 745-750.
80. Ko, L.J. and Prives, C. (1996) p53: puzzle and paradigm. Genes Dev., 10, 1054-1072.
81. Wang, X.W., Forrester, K., Yeh, H., Feitelson, M.A., Gu, J.R. and Harris, C.C. (1994) Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc. Natl Acad. Sci. USA, 91, 2230-2234.
82. Wang, X.W., Yeh, H., Schaeffer, L., Roy, R., Moncollin, V., Egly, J.M., Wang, Z., Freidberg, E.C., Evans, M.K., Taffe, B.G. et al. (1995) p53 modulation of TFIIH-associated nucleotide excision repair activity. Nature Genet., 10, 188-195.
83. Xiao, H., Pearson, A., Coulombe, B., Truant, R., Zhang, S., Regier, J.L., Triezenberg, S.J., Reinberg, D., Flores, O., Ingles, C.J. et al. (1994) Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53. Mol. Cell. Biol., 14, 7013-7024.
84. Leveillard, T., Andern, L., Bissonnette, N., Schaeffer, L., Bracco, L., Egly, J.M. and Wasylyk, B. (1996) Functional interactions between p53 and the TFIIH complex are affected by tumour-associated mutations. EMBO J., 15, 1615-1624.
85. Drapkin, R., Le Roy, G., Cho, H., Akoulitchev, S. and Reinberg, D. (1996) Human cyclin-dependent kinase-activating kinase exists in three distinct complexes. Proc. Natl Acad. Sci. USA, 93, 6488-6493.
86. Marinoni, J.C., Roy, R., Vermeulen, W., Miniou, P., Lutz, Y., Weeda. G., Seroz, T., Gomez, D.M., Hoeijmakers, J.H. and Egly, J.M. (1997) Cloning and characterization of p52, the fifth subunit of the core of the transcription/DNA repair factor TFIIH. EMBO J., 16, 1093-1102.
87. Svejstrup, J.Q., Vichi, P. and Egly, J.M. (1996) The multiple roles of transcription/repair factor TFIIH. Trends Biochem. Sci., 21, 346-350.
88. Lindahl, T., Karran, P. and Wood, R.D. (1997) DNA excision repair pathways. Curr. Opin. Genet. Dev., 7, 158-169.
89. Lee, S., Elenbaas, B., Levine, A. and Griffith, J. (1995) p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell, 81, 1013-1020.
90. Sutherland, G.R. and Richards, R.I. (1995) The molecular basis of fragile sites in human chromosomes. Curr. Opin. Genet. Dev., 5, 323-327.
91. Baker, J.S., Markowitz, S., Fearon, R.E., Willson, V.K.J. and Vogelstein, B. (1992) Suppression of human colorectal carcinoma cell growth by wild-type p53. Science, 249, 912-915.
92. Kern, E.S., Pietenpol, J.A.,Thiagalingam, S., Seymour, A., Kinzler,W.K. and Vogelstein, B. (1992) Oncogenic forms of p53 inhibit p53 regulated gene expression. Science, 256, 827-830.
93. Linke, S.P., Clarkin, K.C., Di Leonardo, A., Tsou, A. and Wahl, G.M. (1996) A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev., 10, 934-947.
94. Anderson, M.J., Casey, G., Fasching, C.L. and Stanbridge, E.J. (1994) Evidence that wild-type TP53, and not genes on either chromosome 1 or 11, controls the tumorigenic phenotype of the human fibrosarcoma HT1080. Genes Chromosomes Cancer, 9, 266-281.
95. Sharma, S., Schwarte-Waldhoff, I., Oberhuber, H. and Schafer, R. (1993) Functional interaction of wild-type and mutant p53 transfected into human tumor cell lines carrying activated ras genes. Cell Growth Differ., 4, 861-869.
96. Pellegata, N.S., Antoniono, R.J., Redpath, J.L. and Stanbridge, E.L. (1996) DNA damage and p53-mediated cell cycle arrest: a reevaluation. Proc. Natl Acad. Sci. USA, 93, 15209-15214.
97. Chen, P.L., Chen, Y.M., Bookstein, R. and Lee, W.H. (1990) Genetic mechanisms of tumor suppression by the human p53 gene. Science, 250, 1576-1580.
98. Lim, K. and Chae, C.B. (1989) A simple assay for DNA transfection by incubation of the cells in culture dishes with substrates for β-galactosidase. BioTechniques. 7, 576-579.
99. Friedlander, P., Legros, Y., Soussi, T. and Prives, C. (1996) Regulation of mutant p53 temperature-sensitive DNA binding. J. Biol. Chem., 271, 25468-25478.
100. Ma, C., Martin, S., Trask, B. and Hamlin, J.L. (1996) Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells. Genes Dev., 7, 605-620.