Histone deacetylase inhibitors and genomic instability.
Histone deacetylase inhibitors (HDACIs) are a promising new class of anticancer drugs. However, their mechanism of action has not been fully elucidated. Most studies have investigated the effect of HDACIs on the regulation of gene transcription. HDAC inhibition also leads to genomic instability by a variety of mechanisms. This phenomenon, which has been largely overlooked, may contribute to the cytotoxic effects of these drugs. Indeed, HDACIs sensitize DNA to exogenous genotoxic damage and induce the generation of reactive oxygen species. Moreover, HDACIs target mitosis resulting in chromosome segregation defects. Here, we review the effects of HDACI treatment on DNA damage and repair, and chromosome segregation control.
Eot-Houllier
Grégory
G
Groupe Microtubules et Cycle Cellulaire, Institut de Génétique Humaine, CNRS UPR 1142, rue de la cardonille, 34396 Montpellier cedex 5, France.
Fulcrand
Géraldine
G
Magnaghi-Jaulin
Laura
L
Jaulin
Christian
C
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D042822:Genomic Instability; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D018384:Oxidative Stress
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors