DECREASED EXPRESSION OF TOPOISOMERASE II-BETA 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 resp onse to various genomic insults. In the absence of DNA damaging treatm ent, we report here that a PARP-deficient cell line (PARP-/-) establis hed from knockout mice displays a decrease in topoisomerase II (topo I I) activity as measured by decatenation of kinetoplast DNA, Immunoblot ting of whole and nuclear cell extracts showed that reduced activity w as associated with decreased amount of the 180 kDa topo II beta protei n but not of the 170 kDa topo II alpha. The decreased topo II beta exp ression did not stem from transcriptional regulation of gene expressio n since levels of topo II beta mRNA were similar in PARR (-/-) compare d with the parental PARP (+/+) cells. The decreased topo II activity w as 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 II beta.