Topoisomerase inhibitor induced dephosphorylation of H1 and H3 histones as a consequence of cell cycle arrest.
Posttranslational modifications of histones have an integral function in the structural and functional organization of chromatin. Several changes in the modification state of histones could be observed after induction of apoptosis with topoisomerase inhibitors and other inducers. Most of these studies include the analysis of the state of phosphorylation of histones, and the results are to some extent controversial, depending on cell lines and agents used. In the present study we compared the kinetics of the dephosphorylation of H1 and H3 histones with apoptosis markers after treatment of leukemic cell lines with topoisomerase inhibitors. In parallel, we determined cell cycle parameters in detail. Dephosphorylation of both histone classes started within 1 h of induction, and no direct correlation with timing and intensity of the investigated apoptotic features could be observed. In contrast, we show that the effect of topoisomerase inhibitors on the state of H1 and H3 phosphorylation is not directly related to apoptosis, but reflects the changes in the cell cycle distribution of cells treated with these inducers.
Happel
Nicole
N
Institute for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany. nhappel@gwdg.de
Sommer
Arne
A
Hänecke
Kristina
K
Albig
Werner
W
Doenecke
Detlef
D
D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D026942:DNA Topoisomerases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D059003:Topoisomerase Inhibitors
D004791:Enzyme Inhibitors; D006657:Histones; D059003:Topoisomerase Inhibitors; D026942:DNA Topoisomerases