Abstract
Cloned genomic DNA for human histone H1, H3 and H4 genes has been used to determine the effects of γ-radiation on histone mRNA levels and synthesis in ataxia-telangiectasia cells. Synthesis of histone mRNA was determined in cells synchronized with aphidicolin. Effects of irradiation on DNA synthesis and passage through S phase were also monitored. Irradiation was found to slow the passage of control cells through the cell cycle but had no effect on progression of ataxia-telangiectasia cells. H1 and core histone mRNA synthesis was inhibited by radiation in two control cell lines after release from aphidicolin block. No inhibition was observed in one ataxia-telangiectasia cell line and a small degree of inhibition in a second. An increased level of mRNA was observed in both irradiated control and ataxia-telangiectasia cells at 5–7 h post-irradiation compared to unirradiated cells. Similar results were obtained in log phase cells. These results demonstrate that histone mRNA synthesis is radioresistant in ataxia-telangiectasia cells and is coupled to radioresistant DNA synthesis in these cells.
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Robbins E, Borun TW: The cytoplasmic synthesis of histones in HeLa cells and its temporal relationship to DNA replication. Proc Natl Acad Sci USA 57:409–416, 1967.
Spalding J, Kajiwara K, Mueller GL: The metabolism of basic proteins in HeLa cell nuclei. Proc Natl Acad Sci USA 56:1535–1542, 1966.
McGhee JD, Felsenfeld G: Nucleosome structure. Ann Rev Biochem 49:1115–1156, 1980.
Hereford LM, Osley MA, Ludwig II JR, McLaughlin CS: Cell cycle regulation of yeast histone mRNA. Cell 24:367–375, 1981.
Marashi F, Baumbach L, Rickles R, Sierra F, Stein JL, Stein S: Histone proteins in HeLa S3 cells are synthesized in a cell cycle stage-specific manner. Science 215:683–685, 1982.
Plumb M, Stein J, Stein G: Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. Nucl Acids Res 11:2391–2410, 1983.
Heintz N, Zernik M, Roeder RG: The structure of the human histone genes: Clustered but not tandemly repeated. Cell 24:661–668, 1981.
Hereford LM, Bromley S, Osley MA: Periodic transcription of yeast histone genes. Cell 30:305–310, 1982.
Sierra F, Lichtler A, Marashi F, Rickles R, van Dyke T, Clark S, Wells J, Stein G, Stein J: Organization of human histone genes. Proc Natl Acad Sci USA 79:1795–1799, 1982.
Sittman DB, Graves RA, Marzluff WF: Histone mRNA concentrations are regulated at the level of transcription and mRNA degradation. Proc Natl Acad Sci USA 80:1849–1853, 1983.
Breindl M, Gallwitz D: On the translational control of histone sequences. Quantitation of biologically active histone mRNA from synchronized HeLa cells and its translation in different cell-free systems. Eur J Biochem 45:91–97, 1973.
Shephard EA, Phillips IR, Davis J, Stein JL, Stein GS: Evidence for the resumption of DNA replication prior to histone synthesis in HeLa cells after release from treatment with hydroxyurea. FEBS Lett 140:189–192, 1982.
Heintz N, Sive HL, Roeder RG: Regulation of human histone gene expression — Kinetics of accumulation and changes in the rate of synthesis. Mol Cell Biol 3:539–550, 1983.
Baumbach LL, Marashi F, Plumb M, Stein G, Stein J: Inhibition of DNA replication coordinately reduces cellular levels of core and H1 histone mRNAs: Requirement for protein synthesis. Biochemistry 23:1618–1625, 1984.
Stein GS, Park WD, Thrall CL, Mans RJ, Stein JL: Regulation of cell cycle stage-specific transcription of histone genes from chromatin by non-histone chromosomal proteins. Nature 257:764–767, 1975.
de Wit J, Jaspers NGJ, Bootsma D: The rate of DNA synthesis in normal human and ataxia-telangiectasia cells after exposure to X-irradiation. Mutation Res 80:221–226, 1981.
Edwards MJ, Taylor AMR: Unusual levels of (ADP-ribose)n and DNA synthesis in ataxia telangiectasia cells following γ-ray irradiation. Nature 287:745–747, 1980.
Houldsworth J, Lavin MF: Effect of ionizing radiation on DNA synthesis in ataxia telangiectasia. Nucl Acids Res 8:3709–3720, 1980.
Painter RB, Young BR: Radiosensitivity in ataxia-telangiectasia: a new explanation. Proc Natl Acad Sci USA 77:7315–7317, 1980.
Lehmann AR, James MR, Stevens S: Miscellaneous observations on DNA repair in ataxia-telangiectasia. In Bridges BA, Harnden DG (eds). Ataxia-telangiectasia — A Cellular and Molecular Link with Cancer. John Wiley and Sons Ltd, New York, 1982, pp 347–353.
Morris C, Mohamed R, Lavin MF: DNA replication and repair in ataxia telangiectasia cells exposed to bleomycin. Mutation Res 112:67–74, 1983.
Painter RB: Radioresistant DNA synthesis: an intrinsic feature of ataxia telangiectasia. Mutation Res 84:183–190, 1981.
Cohen MM, Simpson SJ: Increased clastogenicity and decreased inhibition of DNA synthesis by neocarcinostatin and tallysomycin in ataxia telangiectasia lymphoid cells. Mutation Res 112:119–128, 1983.
Shiloh Y, Becker Y: Reduced inhibition of replicon initiation and chain elongation by neocarcinostatin in skin fibroblasts from patients with ataxia telangiectasia. Biochim Biophys Acta 721:485–488, 1982.
Taylor AMR, Flude E, Garner CM, Campbell JB, Edwards MJ: Effects of the DNA strand-cleaving agent, streptonigrin on ataxia-telangiectasia cells. Cancer Res 43:2700–2703, 1983.
Plumb M, Marashi F, Green L, Zimmerman A, Zimmerman S, Stein J, Stein G: Cell cycle regulation of human histone H1 mRNA. Proc Natl Acad Sci USA 81:434–438, 1984.
Maniatis T, Jeffrey A, Kleid DG: Nucleotide sequence of the rightward operator of phage λ. Proc Natl Acad Sci USA 72:1184–1188, 1975.
Clewell D, Helinski DR: Properties of a supercoiled deoxyribonucleic acid — protein relaxation complex and strand specificity of the relaxation event. Biochemistry 9:4428–4440, 1970.
Maniatis T, Fritsch EF, Sambrook J: Large-scale isolation of plasmid DNA. In: Molecular cloning, a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1982, pp 86–96.
Ford MD, Martin L, Lavin MF: The effects of ionizing radiation on cell cycle progression in ataxia telangiectasia. Mutation Res 125:115–122, 1984.
Bases R, Mendez F: Dissociation of histone and DNA synthesis in X-irradiated HeLa cells. Exp Cell Res 6:289–294, 1971.
Enger MD, Campbell EW, Walters RA: Effect of ionizing radiation on RNA metabolism in cultured mammalian cells. I. Specific effects during division delay following exposure to x-irradiation. Biochim Biophys Acta 324:120–132, 1973.
Cohen MM, Simpson SJ: Growth kinetics of ataxia telangiectasia lymphoblastoid cells. Cytogenet Cell Genet 28:24–33, 1980.
34. Houldsworth J, Kumar S, Lavin MF: Study of chromatin structure in ataxia-telangiectasia cells. Mol Biol Rep, 1986 (in press).
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Lavin, M.F., Houldsworth, J., Kumar, S. et al. Coupling of histone mRNA levels to radioresistant DNA synthesis in ataxia-telangiectasia cells. Mol Cell Biochem 73, 45–54 (1987). https://doi.org/10.1007/BF00229375
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DOI: https://doi.org/10.1007/BF00229375