Preferential degradation of protein-bound (ADP-ribose)n by nuclear poly(ADP-ribose) glycohydrolase from human placenta.

Poly(ADP-ribose) glycohydrolase, extensively purified to homogeneity from nuclei of human placenta, is composed of a single polypeptide with a molecular mass of 71,000 daltons on sodium dodecyl sulfate-polyacrylamide gel. Judging from its physico-chemical and catalytic properties, the enzyme is similar to the nuclear glycohydrolase (glycohydrolase I), but not to the cytoplasmic glycohydrolase (glycohydrolase II) that has been purified from guinea pig liver (Tanuma, S., Kawashima, K., and Endo, H. (1986) J. Biol. Chem. 261, 965-969; Maruta, H., Inageda, K., Aoki, T., Nishina, H., and Tanuma, S. (1991) Biochemistry 30, 5907-5912). The rates of hydrolysis of (ADP-ribose)n bound to various proteins by the purified nuclear glycohydrolase were higher than those of the corresponding free polymers. Kinetic analyses revealed that the enzyme had more activity toward poly(ADP-ribose) bound to histone H1 or to poly(ADP-ribose) polymerase than toward oligo(ADP-ribose) bound to cytoplasmic proteins from mitochondria or mRNA ribonucleoprotein although the Km and Vmax values were dependent on the chain length (n). In contrast, cytoplasmic glycohydrolase purified from human erythrocytes was more active toward oligo(ADP-ribose) (n = 2.6 or 4.2) bound to the cytoplasmic proteins than to poly(ADP-ribose) (n = 14.6) bound to histone H1, and their kinetic parameters of glycohydrolase II were rather dependent on the acceptor molecules for (ADP-ribose)n. These results suggest that poly(ADP-ribose) glycohydrolase I may play an important role in regulation of poly(ADP-ribosyl)ation levels on chromosomal proteins in nuclei.