Mutations of human DNA topoisomerase I at poly (ADP-ribose) binding sites: Modulation of camptothecin activity by ADP-ribose polymers (Articolo in rivista)

Type
Label
  • Mutations of human DNA topoisomerase I at poly (ADP-ribose) binding sites: Modulation of camptothecin activity by ADP-ribose polymers (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1186/s13046-014-0071-z (literal)
Alternative label
  • Tesauro C.; Graziani G.; Arno B.; Zuccaro L.; Muzi A.; D'Annessa I.; Santori E.; Tentori L.; Leonetti C.; Fiorani P.; Desideri A. (2014)
    Mutations of human DNA topoisomerase I at poly (ADP-ribose) binding sites: Modulation of camptothecin activity by ADP-ribose polymers
    in Journal of experimental & clinical cancer research (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Tesauro C.; Graziani G.; Arno B.; Zuccaro L.; Muzi A.; D'Annessa I.; Santori E.; Tentori L.; Leonetti C.; Fiorani P.; Desideri A. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.scopus.com/inward/record.url?eid=2-s2.0-84908213301&partnerID=q2rCbXpz (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 33 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 1 (literal)
Note
  • Scopu (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Biology and Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), University of Rome 'Tor Vergata', Via della Ricerca Scientifica, Rome, 00133, Italy; Department of Systems Medicine, University of Rome Tor 'Vergata', Via Montpellier 1, Rome, 00133, Italy; Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, Rome, 00158, Italy; Institute of Translational Pharmacology, National Research Council, CNR, Via del Fosso del Cavaliere 100, Rome, 00133, Italy (literal)
Titolo
  • Mutations of human DNA topoisomerase I at poly (ADP-ribose) binding sites: Modulation of camptothecin activity by ADP-ribose polymers (literal)
Abstract
  • Background: DNA topoisomerases are key enzymes that modulate the topological state of DNA through the breaking and rejoining of DNA strands. Human topoisomerase I belongs to the family of poly(ADP-ribose)-binding proteins and is the target of camptothecin derived anticancer drugs. Poly(ADP-ribosyl)ation occurs at specific sites of the enzyme inhibiting the cleavage and enhancing the religation steps during the catalytic cycle. Thus, ADP-ribose polymers antagonize the activity of topoisomerase I poisons, whereas PARP inhibitors increase their antitumor effects. Methods: Using site-directed mutagenesis we have analyzed the interaction of human topoisomerase I and poly (ADP-ribose) through enzymatic activity and binding procedures. Results: Mutations of the human topoisomerase I hydrophobic or charged residues, located on the putative polymer binding sites, are not sufficient to abolish or reduce the binding of the poly(ADP-ribose) to the protein. These results suggest either the presence of additional binding sites or that the mutations are not enough perturbative to destroy the poly(ADP-ribose) interaction, although in one mutant they fully abolish the enzyme activity. Conclusions: It can be concluded that mutations at the hydrophobic or charged residues of the putative polymer binding sites do not interfere with the ability of poly(ADP-ribose) to antagonize the antitumor activity of topoisomerase I poisons. (literal)
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