Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells

Qiu, Ling, Burgess, Andrew, Fairlie, David P., Leonard, Helen, Parsons, Peter G. and Gabrielli, Brian G. (2000) Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells. Molecular Biology of the Cell, 11 6: 2069-2083.

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Author Qiu, Ling
Burgess, Andrew
Fairlie, David P.
Leonard, Helen
Parsons, Peter G.
Gabrielli, Brian G.
Title Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells
Journal name Molecular Biology of the Cell   Check publisher's open access policy
ISSN 1059-1524
1939-4586
Publication date 2000-06
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 11
Issue 6
Start page 2069
End page 2083
Total pages 15
Place of publication Bethesda, MD, United States
Publisher American Society for Cell Biology
Collection year 2000
Language eng
Abstract Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic integrity. An increasing number of tumor suppressors are being demonstrated to have roles in checkpoint mechanisms, implying that checkpoint dysfunction is likely to be a common feature of cancers. Here we report that histone deacetylase inhibitors, in particular azelaic bishydroxamic acid, triggers a G2 phase cell cycle checkpoint response in normal human cells, and this checkpoint is defective in a range of tumor cell lines. Loss of this G2 checkpoint results in the tumor cells undergoing an aberrant mitosis resulting in fractured multinuclei is and micronuclei and eventually cell death. This histone deacetylase inhibitor-sensitive checkpoint appears to be distinct from G2/M checkpoints activated by genotoxins and microtubule poisons and may be the human homologue of a yeast G2 checkpoint, which responds to aberrant histone acetylation states. Azelaic bishydroxamic acid may represent a new class of anticancer drugs with selective toxicity based on its ability to target a dysfunctional checkpoint mechanism in tumor cells.
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Tue, 10 Jun 2008, 13:11:44 EST