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Interaction of calf thymus poly(ADP-ribose(ADPR] polymerase with a copurified DNA fraction (sDNA) was investigated. Electron microscopic studies of sDNA which appeared to be a powerful poly(ADPR) polymerase activator have shown that the purified poly(ADPR) polymerase-DNA complexes possess a "nucleosome like structure", with DNA wrapping around the enzyme molecule. Examination of the DNA linked poly(ADPR) polymerase preparations revealed the presence of Y-structures in sDNA. The enrichment in the sDNA fraction of the Y shape DNA suggests the existence of replication fork structures in the poly(ADPR) polymerase linked DNA and or in the vicinity of the enzyme. With increasing auto-poly(ADP-ribosyl)ation the enzyme molecule becomes much denser, increases in size and detaches from the DNA. When poly(ADPR) formed was purified and examined by electron microscopy, branched polymers of different sizes were observed. The formation of these polymers may explain the size gained by poly ADP-ribosylated enzyme molecules. When the interaction of poly(ADPR) polymerase with the plasmid pBR 322 was tested, a slight contamination of our enzyme preparation with topoisomerase I was detected. The contaminant topoisomerase I activity, however, was completely abolished by ADP-ribosylation. Further experiments with purified calf thymus topoisomerase I confirmed that this enzyme loses its activity following ADP-ribosylation with poly(ADPR) polymerase. These results may suggest that ADP-ribosylation of topoisomerase I can be one of the regulatory mechanisms of its activity. Furthermore, these results confirm that a topoisomerase I contaminant does not interfere with the ADP-ribosylation experiments of purified poly(ADPR) polymerase preparation.

The characteristics of 5HT2 receptor binding were investigated in major depression in vivo using positron emission tomography and the radioligand F-18-altanserin.Twelve patients from families with high loading of depression living in a geographically restricted region were examined and compared with normal control subjects. At the time of the PET measurement all patients were remitted; in some of them remission was sustained by antidepressive medication. Binding potential was assessed by Logan's graphical analysis method.The binding of F-18-altanserin was about 38% lower in patients than in healthy controls (p0.001). A multiple regression analysis revealed that this difference was mainly induced by depression rather than by medication.The data suggest that 5HT2 receptors are altered in depression. We present evidence for a reduction of the receptor density, which might be usable as trait marker of subjects susceptible for depressive illness.