Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Feb 1;90(3):853–857. doi: 10.1073/pnas.90.3.853

Apoptosis in C3H/10T1/2 mouse embryonic cells: evidence for internucleosomal DNA modification in the absence of double-strand cleavage.

L D Tomei 1, J P Shapiro 1, F O Cope 1
PMCID: PMC45768  PMID: 8430096

Abstract

Apoptosis in embryonic C3H/10T1/2 (clone 8) cells is marked by specific changes in morphology and DNA fragmentation that differ from those found in apoptotic thymocytes. These results demonstrate that ultrastructural changes within the nucleus associated with endonucleolytic degradation are linked with structural degradation at higher levels of chromatin organization. Strand modifications within the internucleosomal linker region are shown to involve alkaline-sensitive sites that appear to be sensitive to S1 endonuclease. Our results suggest that apoptosis is not dependent upon internucleosomal cleavage and may reveal the penultimate step and the nature of the metabolic cascade that leads to cell death.

Full text

PDF
853

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arends M. J., Morris R. G., Wyllie A. H. Apoptosis. The role of the endonuclease. Am J Pathol. 1990 Mar;136(3):593–608. [PMC free article] [PubMed] [Google Scholar]
  2. Duke R. C., Cohen J. J. IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells. Lymphokine Res. 1986 Fall;5(4):289–299. [PubMed] [Google Scholar]
  3. Fortini P., Bignami M., Dogliotti E. Evidence for AP site formation related to DNA-oxygen alkylation in CHO cells treated with ethylating agents. Mutat Res. 1990 Jul;236(1):129–137. doi: 10.1016/0921-8777(90)90040-c. [DOI] [PubMed] [Google Scholar]
  4. Gromkowski S. H., Brown T. C., Cerutti P. A., Cerottini J. C. DNA of human Raji target cells is damaged upon lymphocyte-mediated lysis. J Immunol. 1986 Feb 1;136(3):752–756. [PubMed] [Google Scholar]
  5. Kanter P., Leister K. J., Tomei L. D., Wenner P. A., Wenner C. E. Epidermal growth factor and tumor promoters prevent DNA fragmentation by different mechanisms. Biochem Biophys Res Commun. 1984 Jan 30;118(2):392–399. doi: 10.1016/0006-291x(84)91315-9. [DOI] [PubMed] [Google Scholar]
  6. Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kruman I. I., Matylevich N. P., Beletsky I. P., Afanasyev V. N., Umansky S. R. Apoptosis of murine BW 5147 thymoma cells induced by dexamethasone and gamma-irradiation. J Cell Physiol. 1991 Aug;148(2):267–273. doi: 10.1002/jcp.1041480212. [DOI] [PubMed] [Google Scholar]
  8. Laval J., Boiteux S., O'Connor T. R. Physiological properties and repair of apurinic/apyrimidinic sites and imidazole ring-opened guanines in DNA. Mutat Res. 1990 Nov-Dec;233(1-2):73–79. doi: 10.1016/0027-5107(90)90152-t. [DOI] [PubMed] [Google Scholar]
  9. Lyamichev V. I., Mirkin S. M., Frank-Kamenetskii M. D. A pH-dependent structural transition in the homopurine-homopyrimidine tract in superhelical DNA. J Biomol Struct Dyn. 1985 Oct;3(2):327–338. doi: 10.1080/07391102.1985.10508420. [DOI] [PubMed] [Google Scholar]
  10. Nejedlý K., Matyásek R., Palecek E. Site-specific chemical modification of B-Z junctions in supercoiled DNA as detected by nuclease S1 digestion, inhibition of restriction cleavage and nucleotide sequencing. J Biomol Struct Dyn. 1988 Oct;6(2):261–275. doi: 10.1080/07391102.1988.10507712. [DOI] [PubMed] [Google Scholar]
  11. Raff M. C. Social controls on cell survival and cell death. Nature. 1992 Apr 2;356(6368):397–400. doi: 10.1038/356397a0. [DOI] [PubMed] [Google Scholar]
  12. Tomei L. D., Kanter P., Wenner C. E. Inhibition of radiation-induced apoptosis in vitro by tumor promoters. Biochem Biophys Res Commun. 1988 Aug 30;155(1):324–331. doi: 10.1016/s0006-291x(88)81088-x. [DOI] [PubMed] [Google Scholar]
  13. Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]
  14. Zlatanova J., Yaneva J. Histone H1-DNA interactions and their relation to chromatin structure and function. DNA Cell Biol. 1991 May;10(4):239–248. doi: 10.1089/dna.1991.10.239. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES