Age-dependent increase of DNA topoisomerase II activity in quail oviduct; modulation of the nuclear matrix-associated enzyme activity by protein phosphorylation and poly(ADP-ribosyl)ation.
Nuclear DNA topoisomerase II activity in quail oviduct tissue was found to increase by about 70% with age. This age-dependent increase was observed with both the enzyme in whole nuclear extract and nuclear matrix-associated topoisomerase II. Both purified topoisomerase II and the nuclear matrix-bound enzyme were found to be modifiable by phosphorylation and poly(ADP-ribosyl)ation. Phosphorylation of the purified enzyme by isolated nuclear protein kinase NII or protein kinase C resulted in a 2- to 3-fold increase in specific activity, while poly(ADP-ribosyl)ation by soluble poly(ADP-ribose) synthetase caused a 50% inhibition of the enzyme. Using immunoprecipitation and immunoblotting procedures, phosphorylation and poly(ADP-ribosyl)ation could also be demonstrated to occur with the nuclear matrix-associated enzyme. The nuclear matrix-associated NII-like protein kinase activity, assumed to be involved in post-translational modification of topoisomerase II, displayed a 1.4- to 1.6-fold increase in old animals compared to mature ones, while the matrix-bound poly(ADP-ribose) synthetase activity decreased by about 50%. It is suggested that age-correlated enhancement of DNA topoisomerase II activity, possibly due to age-dependent changes in activities of nuclear protein kinases and poly(ADP-ribose) synthetase, may result in alterations in the topological state of DNA, possibly affecting DNA replication, transcription and repair with age.
Schröder
H C
HC
Institut für Physiologische Chemie, Universität, Mainz, F.R.G.
Steffen
R
R
Wenger
R
R
Ugarković
D
D
Müller
W E
WE
D000375:Aging; D000818:Animals; D003370:Coturnix; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D009243:NAD / Q000378:metabolism; D015530:Nuclear Matrix / Q000201:enzymology; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D010057:Oviducts / Q000201:enzymology / Q000254:growth & development*; D010766:Phosphorylation; D010957:Plasmids; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D009702:Nucleoside Diphosphate Sugars; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases; D004250:DNA Topoisomerases, Type II