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

Taylor, Elaine M. and McFarlane, R.J. and Price, Clive (1996) 5-Azacytidine treatment of the fission yeast leads to cytotoxicity and cell cycle arrest. Molecular and General Genetics, 253 (1-2). pp. 128-137.

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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.

Item Type: Article
Journal or Publication Title: Molecular and General Genetics
Uncontrolled Keywords: Fission yeast ; 5-Azacytidine ; DNA methylation ; Checkpoint controls
Subjects:
Departments: Faculty of Health and Medicine > Medicine
Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 60125
Deposited By: ep_importer_pure
Deposited On: 26 Nov 2012 14:21
Refereed?: Yes
Published?: Published
Last Modified: 26 Nov 2012 14:21
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/60125

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