Poly nuclear matrix associated

Altogether, these observations suggest the occurrence poly(ADP-ribose) metabolism in two compartments of chromatin one that is nuclear matrix-associated and one that is not. The elucidation of the biological significance of this compartmentalization awaits further information concerning the molecules which interact with the polymers in both compartments. 

Burlde A (2005) Poly(ADP-ribose). The most elaborate metabolite of NAD. Febs J 272 4576-4589 Burlde A, Brabeck C, Diefenbach J, Beneke S (2005) The emerging role of poly(ADP-ribose) polymerase-1 in longevity. Int J Biochem Cell Biol 37 1043—1053 Cardenas-Corona M, Jacobson E, Jacobson M (1987) Endogenous polymers of ADP-ribose are associated with the nuclear matrix. J Biol Chem 262 14863—14866 Chang P, Jacobson MK, Mitchison TJ (2004) Poly(ADP-ribose) is required for spindle assembly and structure. Nature 432 645-649... 

ADP-Ribosylation of Nuclear Matrix Proteins. Association of Poly(ADP-Ribose) Synthetase with the Nuclear Matrix... 

The present experiments show that a number of ADP-ribosylated proteins in the range of 40,000-300,000 kD exist in nuclear matrices isolated from HeLa cells, and that the lamins A and B are probably modified. Furthermore, it was observed that a portion (approx. 1%) of the nuclear poly(ADP-ribose) synthetase is tightly associated with the isolated nuclear matrix. 

The present results demonstrate that a portion of the nuclear poly(ADP-ribose) synthetase is found in tight association with the isolated nuclear matrix. The question is whether the enzyme, if present at this site in vivo, is required to maintain reactions proceeding in association with the nuclear matrix. These may, for example, be reactions involving DNA in the vicinity of the DNA attachment sites. In view of various indications that transcription of active genes occurs in association with the nuclear matrix [6-9], the results of Slattery et al. [27] are also of interest. The authors observed that poly(ADP-ribose) synthetase is identical with the factor TFIIC which, by inhibiting nick-induced transcription, eliminates random transcription by polymerase II. 

Are ADP-ribose polymers randomly or non randomly distributed in chromatin Isolated nuclei from hyperthermia-MNNG-treated ceUs were digested with MNase and the DNA and poly(ADP-ribose) released into the digestion supernatant were determined. While 80% of the total DNA was rendered soluble by the nuclease, 90% of the total ADP-ribose residues remained with the MNase resistant chromatin (Fig 1). These data show that ADP-ribose polymers are not randomly distributed in chromatin but rather they exhibit a predominant association with the chromatin fraction which was resistant to MNase digestion. However the possibility that these polymers confer resistance to the nuclease digestion can not be ruled out at this point. The MNase resistant chromatin fraction isolated in these experiments contained approximately 20% of the total DNA and proteins that isolate with the nuclear matrix. TTius, the possibility of the association of ADP-ribose polymers with the nuclear matrix was examined. 

About 50% of the total Poly(ADP-ribose) residues are tightly associated with the nuclear matrix. Nuclear matrices were prepared and the poly(ADP-ribose) content of these preparations was examined. About 50% of the total polymer residues were associated with the nuclear matrices (Table 1). The association of poly(ADP-ribose) to the nuclear matrix could be explained in two ways, either the polymers are associated in vivo or this association occurred in vitro during the cell fractionation. Two independent lines of evidence support an in vivo association i) exogenous polymers added to isolated nuclei prior to the preparation of nuclear matrices did not bind significantly to these matrices ii) nuclear matrices isolated by... 

In contrast to the high poly(ADP-ribose) content of the nuclear matrix, its DNA content was less than 1% of the total (Table 1). This result raises the interesting possibility that 50% of the total poly(ADP-ribose) is associated with a chromatin fraction which is clustered and tightly bound to the nuclear matrix. However, this possibility has to be reconciled wifli the observation that the fraction of poly(ADP-ribose) released from the nuclei by salt extraction was not dependent on prior nuclease digestion, since approximately the same fraction of polymers was released by salt extraction of undigested nuclei (Table 1). 

Fig. 2. Molecular sieve chromatography of non-matrix and matrix-associated ADP-ribose polymers. Radiolabeled ADP-iibose jwlymers isolated from the nuclear matrix (upper panel) and salt extract (lower panel). The peaks for the positions of non radiolabeled standards of poly A, (Ap)iiA (12), (Ap)vA (8), (Ap)4A (5), ADP-ribose and AMP (1)...

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