Specific inhibition of Physarum polycephalum DNA-polymerase-alpha-primase by poly(L-malate) and related polyanions
| Autor: | Eggehard Holler, Bettina Seidel, Michel Vert, Christina Windisch, Christoph Hambach, Philipe Guerin, Christian Braud, Bernhard Angerer, Cornelia Weber, Gunthar Achhammer, Hermine Reisner, Birgit Gantz |
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| Rok vydání: | 1992 |
| Předmět: |
Anions
Nucleosome assembly Stereochemistry DNA polymerase Polymers Malates Spermine Physarum polycephalum DNA Primase Biochemistry Histones chemistry.chemical_compound Structure-Activity Relationship Animals biology DNA synthesis Osmolar Concentration RNA Nucleotidyltransferases biology.organism_classification Spermidine Kinetics chemistry Polyglutamic Acid biology.protein Polyvinyls Primase Peptides DNA |
| Zdroj: | European journal of biochemistry. 206(1) |
| ISSN: | 0014-2956 |
| Popis: | Poly(L-malate) is an unusual polyanion found in nuclei of plasmodia of Physarum polycephalum. We have investigated, by enzymatic and fluorimetric methods, whether poly(L-malate) and structurally related polyanions can interact with DNA-polymerase-alpha-primase complex and with histones of P. polycephalum. Poly(L-malate) is found to inhibit the activities of the DNA-polymerase-alpha-primase complex and to bind to histones. The mode of inhibition is competitive with regard to DNA in elongation and noncompetitive in the priming of DNA synthesis. Spermidine, spermine, and histones from P. polycephalum and from calf thymus bind to poly(L-malate) and antagonize the inhibition. The polyanions poly(vinyl sulfate), poly(acrylate), poly(L-malate), poly(D,L-malate), poly(L-aspartate), poly(L-glutamate) have been examined for their potency to inhibit the DNA polymerase. The degree of inhibition is found to depend on the distance between neighboring charges, given by the number of atoms (N) interspaced between them. Poly(L-malate) (N = 5) and poly(D,L-malate) (N = 5) are the most efficient inhibitors, followed by poly(L-aspartate) (N = 6), poly(acrylate) (N = 3), poly(L-glutamate) (N = 8), poly(vinyl sulfate) (N = 3). It is proposed that poly(L-malate) interacts with DNA-polymerase-alpha-primase of P. polycephalum. According to its physical and biochemical properties, poly(L-malate) may alternatively function as a molecular chaperone in nucleosome assembly in the S phase and as both an inhibitor and a stock-piling agent of DNA-polymerase-alpha-primase in the G2 phase and M phase of the plasmodial cell cycle. |
| Databáze: | OpenAIRE |
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