Molecular and General Genetics MGG

, Volume 253, Issue 1–2, pp 128–137 | Cite as

5-Azacytidine treatment of the fission yeast leads to cytotoxicity and cell cycle arrest

  • E. M. Taylor
  • R. J. McFarlane
  • C. Price
ORIGINAL PAPER

Abstract

 A fission yeast gene which shares considerable sequence homology with cytosine-specific DNA methyltransferases has recently been identified. This discovery has led us to investigate the effects of the treatment of fission yeast with the nucleoside analogue 5-azacytidine (5-azaC). 5-AzaC is known to inhibit cytosine methylation as a result of the formation of stable covalent complexes between DNA (cytosine-5) methyltransferases (C5 Mtases) and 5-azaC containing DNA. Here we demonstrate that 5-azaC treatment of Schizosaccharomyces pombe leads to reversible cell cycle arrest at the G2/M transition. This reversible arrest is dependent on the cell cycle checkpoint mechanisms which act to prevent the onset of mitosis in the presence of either damaged or unreplicated DNA. Treatment of S. pombe cell division cycle and checkpoint mutants indicates that 5-azaC causes DNA damage and is likely to inhibit a late stage in DNA replication. The data show that viability in the presence of the drug requires both the DNA damage and the replication checkpoint pathways to be functional. 5-AzaC also elicits a transcriptional response which is associated with DNA damage and the inhibition of DNA replication in fission yeast, and this response is absent in cells carrying G2 checkpoint mutations. The implications of these observations for both the use of 5-azaC in cancer chemotherapy and the existence of cytosine methylation in fission yeast are discussed.

Key words Fission yeast 5-Azacytidine DNA methylation Checkpoint controls 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • E. M. Taylor
    • 1
  • R. J. McFarlane
    • 1
  • C. Price
    • 1
  1. 1.Krebs Institute for Biomolecular Science, Department of Molecular Biology and Biotechnology, University of Sheffield, P. O. Box 594, Western Bank, Sheffield S10 2UH, UKGB

Personalised recommendations