Decreased expression of topoisomerase IIbeta in poly(ADP-ribose) polymerase-deficient cells.
Recent studies with poly(ADP-ribose) polymerase (PARP)-deficient mice have highlighted the role of this enzyme in genomic stability and response to various genomic insults. In the absence of DNA damaging treatment, we report here that a PARP-deficient cell line (PARP-/-) established from knockout mice displays a decrease in topoisomerase II (topo II) activity as measured by decatenation of kinetoplast DNA. Immunoblotting of whole and nuclear cell extracts showed that reduced activity was associated with decreased amount of the 180 kDa topo IIbeta protein but not of the 170 kDa topo IIalpha. The decreased topo IIbeta expression did not stem from transcriptional regulation of gene expression since levels of topo IIbeta mRNA were similar in PARP (-/-) compared with the parental PARP (+/+) cells. The decreased topo II activity was associated with cell resistance to VP16, a topo II inhibitor. These observations indicate that PARP may play a role in the stabilization and/or distribution of topo IIbeta.
Canitrot
Y
Y
Institut de Pharmacologie et Biologie Structurale, UPR CNRS 9062, 205 route de Narbonne, 31077 Toulouse cedex, France.
de Murcia
G
G
Salles
B
B
D000818:Animals; D002460:Cell Line; D004250:DNA Topoisomerases, Type II / Q000172:deficiency* / Q000235:genetics; D004268:DNA-Binding Proteins; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D018345:Mice, Knockout; D008970:Molecular Weight; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D011065:Poly(ADP-ribose) Polymerases; D004250:DNA Topoisomerases, Type II