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Infection and Immunity, September 2001, p. 5752-5759, Vol. 69, No. 9
Department of Microbiology and
Immunology1 and Department of
Biochemistry and L. P. Markey Cancer
Center,2 College of Medicine, University of
Kentucky, Lexington, Kentucky 40536
Received 2 February 2001/Returned for modification 28 March
2001/Accepted 12 June 2001
Cytolethal distending toxins (CDTs) are multisubunit proteins
produced by a variety of bacterial pathogens that cause enlargement, cell cycle arrest, and apoptosis in mammalian cells. While their function remains uncertain, recent studies suggest that they can act as
intracellular DNases in mammalian cells. Here we establish a novel
yeast model for understanding CDT-associated disease. Expression of the
CdtB subunit in yeast causes a G2/M arrest, as seen in
mammalian cells. CdtB toxicity is not circumvented in yeast genetically
altered to lack DNA damage checkpoint control or that constitutively
promote cell cycle progression via mutant Cdk1, because CdtB causes a
permanent type of damage that results in loss of viability. Finally, we
establish that CDTs are likely to be potent genotoxins, as indicated by
in vivo degradation of chromosomal DNA associated with expression of
CdtB
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.9.5752-5759.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Cytolethal Distending Toxin Demonstrates Genotoxic
Activity in a Yeast Model
suggesting that the varied distribution of CDT in bacteria
implicates many human pathogens as possessors of genotoxic activity.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, College of Medicine, University of
Kentucky, 800 Rose St., Lexington, KY 40536. Phone: (859) 323-5313. Fax: (859) 257-8994. E-mail: cpicket{at}pop.uky.edu.
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