Abstract
p-Fluorophenylalanine (PFPA), an analogue of phenylalanine which may be incorporated into proteins, increases the duration of mitosis. In the present experiments, based upon quantitative analyses of time-lapse cinemicrographic films, brief treatments of cells with PFPA are shown to affect the duration of metaphase in only those cells which enter division during or shortly after treatment. The offspring of cells with prolonged metaphases also tend to have prolonged metaphases. Analyses of the kinetics of the appearance of prolonged metaphases indicate that some protein specifically associated with mitosis is synthesized primarily during a period which corresponds closely to G2. The manner in which the defect is passed on to daughter cells indicates that the protein involved is conserved and reutilized by daughter cells for their subsequent divisions. Comparable experiments performed with low concentrations of puromycin indicate that the major effect of PFPA is due to its incorporation into protein rather than its ability to inhibit protein synthesis. The fact that puromycin-induced effects can also be passed on to daughter cells is interpreted to mean that cells make only specific amounts of some mitosis-associated proteins and that if a cell "inherits" a deficiency in such protein it is not able to compensate for the deficiency.
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Selected References
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- Arrighi F. E., Hsu T. C. Experimental alteration of metaphase chromosome morphology. Effect of actinomycin D. Exp Cell Res. 1965 Aug;39(1):305–308. doi: 10.1016/0014-4827(65)90035-2. [DOI] [PubMed] [Google Scholar]
- BAKER R. S., JOHNSON J. E., FOX S. W. Incorporation of p-fluorophenylalanine into proteins of Lactobacillus arabinosus. Biochim Biophys Acta. 1958 May;28(2):318–327. doi: 10.1016/0006-3002(58)90478-5. [DOI] [PubMed] [Google Scholar]
- BIESELE J. J., JACQUEZ J. A. Mitotic effects of certain amino acid analogs in tissue culture. Ann N Y Acad Sci. 1954 Nov 17;58(7):1276–1287. doi: 10.1111/j.1749-6632.1954.tb45908.x. [DOI] [PubMed] [Google Scholar]
- COHEN G. N., MUNIER R. Effets des analogues structuraux d'aminoacides sur la croissance, la synthèse de protéines et la synthèse d'enzymes chez Escherichia coli. Biochim Biophys Acta. 1959 Feb;31(2):347–356. doi: 10.1016/0006-3002(59)90007-1. [DOI] [PubMed] [Google Scholar]
- COHEN G. N., MUNIER R. Incorporation d'analogues structuraux d'aminoacides dans les protéines bactériennes. Biochim Biophys Acta. 1956 Sep;21(3):592–593. doi: 10.1016/0006-3002(56)90207-4. [DOI] [PubMed] [Google Scholar]
- HOLZ G. G., Jr, RASMUSSEN L., ZEUTHEN E. NORMAL VERSUS SYNCHRONIZED DIVISION IN TETRAHYMENA PYRIFORMIS. A STUDY WITH ANTIMETABOLITES. C R Trav Lab Carlsberg. 1963;33:289–300. [PubMed] [Google Scholar]
- KERRIDGE D. The effect of inhibitors on the formation of flagella by Salmonella typhimurium. J Gen Microbiol. 1960 Dec;23:519–538. doi: 10.1099/00221287-23-3-519. [DOI] [PubMed] [Google Scholar]
- KISHIMOTO S., LIEBERMAN I. SYNTHESIS OF RNA AND PROTEIN REQUIRED FOR THE MITOSIS OF MAMMALIAN CELLS. Exp Cell Res. 1964 Oct;36:92–101. doi: 10.1016/0014-4827(64)90163-6. [DOI] [PubMed] [Google Scholar]
- KRUH J., ROSA J. [Incorporation in vitro of radiocarbon-labelled fluorophenylalanine into the hemoglobin of rabbit reticulocytes]. Biochim Biophys Acta. 1959 Aug;34:561–563. doi: 10.1016/0006-3002(59)90314-2. [DOI] [PubMed] [Google Scholar]
- Kleinfeld R. G., Sisken J. E. Morphological and kinetic aspects of mitotic arrest by and recovery from colcemid. J Cell Biol. 1966 Dec;31(3):369–379. doi: 10.1083/jcb.31.3.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LaBella F. S., Sanwal M. Isolation of nerve endings from the posterior pituitary gland. Electron microscopy of fractions obtained by centrifugation. J Cell Biol. 1965 Jun;25(3 Suppl):179–193. doi: 10.1083/jcb.25.3.179. [DOI] [PubMed] [Google Scholar]
- MUNIER R., COHEN G. N. Incorporation d'analogues structuraux d'aminoacides dans les protéines bactériennes au cours de leur synthèse in vivo. Biochim Biophys Acta. 1959 Feb;31(2):378–391. doi: 10.1016/0006-3002(59)90011-3. [DOI] [PubMed] [Google Scholar]
- Mueller G. C., Kajiwara K. Actinomycin D and p-fluorophenylalanine, inhibitors of nuclear replication in HeLa cells. Biochim Biophys Acta. 1966 Jun 22;119(3):557–565. doi: 10.1016/0005-2787(66)90132-8. [DOI] [PubMed] [Google Scholar]
- RASMUSSEN L., ZEUTHEN E. Cell division and protein synthesis in Tetrahymena, as studied with p-fluorophenylalanine. C R Trav Lab Carlsberg. 1962;32:333–358. [PubMed] [Google Scholar]
- RICHMOND M. H. Immunological properties of exopenicillinase synthesized by Bacillus cereus 569/H in the presence of amino acid analogues. Biochem J. 1960 Oct;77:112–121. doi: 10.1042/bj0770112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SISKEN J. E. The synthesis of nucleic acids and proteins in the nuclei of Tradescantia root tips. Exp Cell Res. 1959 Mar;16(3):602–614. doi: 10.1016/0014-4827(59)90128-4. [DOI] [PubMed] [Google Scholar]
- STANNERS C. P., TILL J. E. DNA synthesis in individual L-strain mouse cells. Biochim Biophys Acta. 1960 Jan 29;37:406–419. doi: 10.1016/0006-3002(60)90496-0. [DOI] [PubMed] [Google Scholar]
- TAYLOR E. W. RELATION OF PROTEIN SYNTHESIS TO THE DIVISION CYCLE IN MAMMALIAN CELL CULTURES. J Cell Biol. 1963 Oct;19:1–18. doi: 10.1083/jcb.19.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tobey R. A., Petersen D. F., Anderson E. C., Puck T. T. Life cycle analysis of mammalian cells. 3. The inhibition of division in Chinese hamster cells by puromycin and actinomycin. Biophys J. 1966 Sep;6(5):567–581. doi: 10.1016/s0006-3495(66)86678-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- VAUGHAN M., STEINBERG D. Biosynthetic incorporation of fluorophenylalanine into crystalline proteins. Biochim Biophys Acta. 1960 May 20;40:230–236. doi: 10.1016/0006-3002(60)91347-0. [DOI] [PubMed] [Google Scholar]
- WESTHEAD E. W., BOYER P. D. The incorporation of p-fluorophenylalanine into some rabbit enzymes and other proteins. Biochim Biophys Acta. 1961 Nov 25;54:145–156. doi: 10.1016/0006-3002(61)90947-7. [DOI] [PubMed] [Google Scholar]
- WOODARD J., GELBER B., SWIFT H. Nucleoprotein changes during the mitotic cycle in Paramecium aurelia. Exp Cell Res. 1961 Mar;23:258–264. doi: 10.1016/0014-4827(61)90036-2. [DOI] [PubMed] [Google Scholar]
- WOODARD J., RASCH E., SWIFT H. Nucleic acid and protein metabolism during the mitotic cycle in Vicia faba. J Biophys Biochem Cytol. 1961 Feb;9:445–462. doi: 10.1083/jcb.9.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
