Poly nonhistone protein acceptors

At present the events triggering and the mechanism controlling muscle differentiation are not well understood they may include changes in chromatin structure, gene amplification, and specific DNA and/or protein modification. One such modification, namely, poly(ADP-ribosyl)ation of nuclear proteins has recently attracted much attention and several studies have indicated that the enzyme poly(ADP-ribose) synthetase plays a role in cellular differentiation [6-9]. This enz)mie is a nuclear chromatin-associated protein which catalyzes covalent modification of both histone and nonhistone protein acceptors (for reviews see [10-13]). The synthetase is activated by DNA strand breaks and it has been suggested that DNA fragmentation and the consequent increase in poly(ADP-ribose) activity are obligatory events for chick muscle differentiation [6]. 

NAD is used in post translational modification of a variety of proteins, nc>tab y some of the proteins of the chromosomes. The chromosomes are composed of DNA, histones, and nonhistone proteins. The histones, which are distinguished by their high content of basic amino acids, serve as a scaffold and maintain the coiled and folded structure of the DNA. The other proteins are used in regulating the expression of specific genes. Poly(ADP-ribose) polymerase catalyzes the attachment of ADP-rlbose to various chromostimal pniteins. This modification, shown in Figure 9.65A, is more dramatic than a simple methylalion or phosphorj lation. The enzyme uses NAD as a substrate. Here, NAD docs not serve its usual role as an Oxidant or reductant. The ADP-ribosyl moiety of NAD is donated to the acceptor protein. A molecule of nicotinamide is discharged with each event of... 

Hayaishi and co-workers (149) were the first to observe that when a nuclear preparation from rat liver was incubated with radiolabeled NAD, the resulting newly synthesized poly(ADP-ribose) was associated with histones Hi, H2A, H2B, and H3 (149). As summarized in the previous section, other groups have corroborated this observation and extended it to include nonhistone nucleosomal proteins (2, 64, 84, 90, 164,178,179, 200, 215, 229). Differences in techniques for isolation of poly ADP-ribosylated proteins and the presence of poly(ADP-ribose) degradative enzymes [poly(ADP-ribose) glycohydrolase and various phosphodiesterases] may explain some of the conflicting reports as to primary acceptor protein, extent of modification, and length of polymer. 

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