Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1994 Aug 11;22(15):3099–3103. doi: 10.1093/nar/22.15.3099

Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum.

M Lanzer 1, S P Wertheimer 1, D de Bruin 1, J V Ravetch 1
PMCID: PMC310281  PMID: 8065922

Abstract

Spontaneous chromosome breakages are frequently observed in the human malaria parasite Plasmodium falciparum and are responsible for the generation of novel phenotypes, which may contribute to the pathogenicity and virulence of this protozoan parasite. The identification of a hot spot of chromosome breakage within the coding region of the KAHRP gene revealed that these events do not occur randomly but follow a regular pattern with a periodicity of 155 bp. This phasing corresponds to the average repeat unit of P. falciparum nucleosomes. Furthermore, breakage events preferentially occur within the linker regions of nucleosomes, as demonstrated by mapping endonuclease hypersensitive sites of chromatin. These data suggest that, in P. falciparum, the chromatin structure is involved in the molecular process of chromosome breakage, a mechanism that may be common in other eukaryotes.

Full text

PDF
3102

Images in this article

3100Image
on p.3100
3101Image
on p.3101

Selected References

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

  1. Adams C. C., Workman J. L. Nucleosome displacement in transcription. Cell. 1993 Feb 12;72(3):305–308. doi: 10.1016/0092-8674(93)90109-4. [DOI] [PubMed] [Google Scholar]
  2. Barnwell J. W. Cytoadherence and sequestration in falciparum malaria. Exp Parasitol. 1989 Nov;69(4):407–412. doi: 10.1016/0014-4894(89)90190-2. [DOI] [PubMed] [Google Scholar]
  3. Borst P., Greaves D. R. Programmed gene rearrangements altering gene expression. Science. 1987 Feb 6;235(4789):658–667. doi: 10.1126/science.3544215. [DOI] [PubMed] [Google Scholar]
  4. Bresnick E. H., Bustin M., Marsaud V., Richard-Foy H., Hager G. L. The transcriptionally-active MMTV promoter is depleted of histone H1. Nucleic Acids Res. 1992 Jan 25;20(2):273–278. doi: 10.1093/nar/20.2.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark D. J., Felsenfeld G. A nucleosome core is transferred out of the path of a transcribing polymerase. Cell. 1992 Oct 2;71(1):11–22. doi: 10.1016/0092-8674(92)90262-b. [DOI] [PubMed] [Google Scholar]
  6. Collins K., Greider C. W. Tetrahymena telomerase catalyzes nucleolytic cleavage and nonprocessive elongation. Genes Dev. 1993 Jul;7(7B):1364–1376. doi: 10.1101/gad.7.7b.1364. [DOI] [PubMed] [Google Scholar]
  7. Creedon K. A., Kaslow D. C., Rathod P. K., Wellems T. E. Identification of a Plasmodium falciparum histone 2A gene. Mol Biochem Parasitol. 1992 Aug;54(1):113–115. doi: 10.1016/0166-6851(92)90102-p. [DOI] [PubMed] [Google Scholar]
  8. Gottesfeld J. M., Melton D. A. The length of nucleosome-associated DNA is the same in both transcribed and nontranscribed regions of chromatin. Nature. 1978 May 25;273(5660):317–319. doi: 10.1038/273317a0. [DOI] [PubMed] [Google Scholar]
  9. Harrington L. A., Greider C. W. Telomerase primer specificity and chromosome healing. Nature. 1991 Oct 3;353(6343):451–454. doi: 10.1038/353451a0. [DOI] [PubMed] [Google Scholar]
  10. Kemp D. J., Corcoran L. M., Coppel R. L., Stahl H. D., Bianco A. E., Brown G. V., Anders R. F. Size variation in chromosomes from independent cultured isolates of Plasmodium falciparum. Nature. 1985 May 23;315(6017):347–350. doi: 10.1038/315347a0. [DOI] [PubMed] [Google Scholar]
  11. Lanzer M., de Bruin D., Ravetch J. V. Transcriptional differences in polymorphic and conserved domains of a complete cloned P. falciparum chromosome. Nature. 1993 Feb 18;361(6413):654–657. doi: 10.1038/361654a0. [DOI] [PubMed] [Google Scholar]
  12. Morin G. B. Recognition of a chromosome truncation site associated with alpha-thalassaemia by human telomerase. Nature. 1991 Oct 3;353(6343):454–456. doi: 10.1038/353454a0. [DOI] [PubMed] [Google Scholar]
  13. Nacheva G. A., Guschin D. Y., Preobrazhenskaya O. V., Karpov V. L., Ebralidse K. K., Mirzabekov A. D. Change in the pattern of histone binding to DNA upon transcriptional activation. Cell. 1989 Jul 14;58(1):27–36. doi: 10.1016/0092-8674(89)90399-1. [DOI] [PubMed] [Google Scholar]
  14. Pologe L. G., Pavlovec A., Shio H., Ravetch J. V. Primary structure and subcellular localization of the knob-associated histidine-rich protein of Plasmodium falciparum. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7139–7143. doi: 10.1073/pnas.84.20.7139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pologe L. G., Ravetch J. V. A chromosomal rearrangement in a P. falciparum histidine-rich protein gene is associated with the knobless phenotype. 1986 Jul 31-Aug 6Nature. 322(6078):474–477. doi: 10.1038/322474a0. [DOI] [PubMed] [Google Scholar]
  16. Pologe L. G., Ravetch J. V. Large deletions result from breakage and healing of P. falciparum chromosomes. Cell. 1988 Dec 2;55(5):869–874. doi: 10.1016/0092-8674(88)90142-0. [DOI] [PubMed] [Google Scholar]
  17. Pologe L. G., de Bruin D., Ravetch J. V. A and T homopolymeric stretches mediate a DNA inversion in Plasmodium falciparum which results in loss of gene expression. Mol Cell Biol. 1990 Jun;10(6):3243–3246. doi: 10.1128/mcb.10.6.3243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Raventos-Suarez C., Kaul D. K., Macaluso F., Nagel R. L. Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3829–3833. doi: 10.1073/pnas.82.11.3829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Roberts D. J., Craig A. G., Berendt A. R., Pinches R., Nash G., Marsh K., Newbold C. I. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992 Jun 25;357(6380):689–692. doi: 10.1038/357689a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Scherf A., Carter R., Petersen C., Alano P., Nelson R., Aikawa M., Mattei D., Pereira da Silva L., Leech J. Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis. EMBO J. 1992 Jun;11(6):2293–2301. doi: 10.1002/j.1460-2075.1992.tb05288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scherf A., Mattei D. Cloning and characterization of chromosome breakpoints of Plasmodium falciparum: breakage and new telomere formation occurs frequently and randomly in subtelomeric genes. Nucleic Acids Res. 1992 Apr 11;20(7):1491–1496. doi: 10.1093/nar/20.7.1491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shirley M. W., Biggs B. A., Forsyth K. P., Brown H. J., Thompson J. K., Brown G. V., Kemp D. J. Chromosome 9 from independent clones and isolates of Plasmodium falciparum undergoes subtelomeric deletions with similar breakpoints in vitro. Mol Biochem Parasitol. 1990 Apr;40(1):137–145. doi: 10.1016/0166-6851(90)90087-3. [DOI] [PubMed] [Google Scholar]
  23. Studitsky V. M., Clark D. J., Felsenfeld G. A histone octamer can step around a transcribing polymerase without leaving the template. Cell. 1994 Jan 28;76(2):371–382. doi: 10.1016/0092-8674(94)90343-3. [DOI] [PubMed] [Google Scholar]
  24. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  25. Udeinya I. J., Schmidt J. A., Aikawa M., Miller L. H., Green I. Falciparum malaria-infected erythrocytes specifically bind to cultured human endothelial cells. Science. 1981 Jul 31;213(4507):555–557. doi: 10.1126/science.7017935. [DOI] [PubMed] [Google Scholar]
  26. Van der Ploeg L. H., Smits M., Ponnudurai T., Vermeulen A., Meuwissen J. H., Langsley G. Chromosome-sized DNA molecules of Plasmodium falciparum. Science. 1985 Aug 16;229(4714):658–661. doi: 10.1126/science.3895435. [DOI] [PubMed] [Google Scholar]
  27. Vernick K. D., McCutchan T. F. Sequence and structure of a Plasmodium falciparum telomere. Mol Biochem Parasitol. 1988 Mar;28(2):85–94. doi: 10.1016/0166-6851(88)90055-2. [DOI] [PubMed] [Google Scholar]
  28. Wilkie A. O., Lamb J., Harris P. C., Finney R. D., Higgs D. R. A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n. Nature. 1990 Aug 30;346(6287):868–871. doi: 10.1038/346868a0. [DOI] [PubMed] [Google Scholar]
  29. Wright J. H., Gottschling D. E., Zakian V. A. Saccharomyces telomeres assume a non-nucleosomal chromatin structure. Genes Dev. 1992 Feb;6(2):197–210. doi: 10.1101/gad.6.2.197. [DOI] [PubMed] [Google Scholar]
  30. Wu T. C., Lichten M. Meiosis-induced double-strand break sites determined by yeast chromatin structure. Science. 1994 Jan 28;263(5146):515–518. doi: 10.1126/science.8290959. [DOI] [PubMed] [Google Scholar]
  31. de Bruin D., Lanzer M., Ravetch J. V. Characterization of yeast artificial chromosomes from Plasmodium falciparum: construction of a stable, representative library and cloning of telomeric DNA fragments. Genomics. 1992 Oct;14(2):332–339. doi: 10.1016/s0888-7543(05)80223-x. [DOI] [PubMed] [Google Scholar]
  32. van Holde K. E., Lohr D. E., Robert C. What happens to nucleosomes during transcription? J Biol Chem. 1992 Feb 15;267(5):2837–2840. [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES