title: Lack of discrimination between DNA ligases I and III by two classes of inhibitors, anthracyclines and distamycins.
abstract: We have measured the effects of eight distamycin and two anthracycline derivatives on polynucleotide joining and self-adenylating activities of human DNA ligase I and rat DNA ligases I and III. All test drugs show good inhibitory activity against the three enzymes in the poly[d(A-T)] joining assay. Several distamycins also inhibit the DNA-independent self-adenylation reaction catalysed by the human enzyme and, to a lesser extent, by rat DNA ligases. These results confirm that anthracyclines and distamycins express their inhibitory action against DNA joining activities mainly via specific interactions with the substrate, and suggest that the three test DNA ligases utilize similar, if not identical, mechanisms of recognition and interaction with DNA-drug complexes. Our findings also indicate that distamycins have a greater affinity for human DNA ligase I than for rat enzymes, suggesting that, in this respect, rat DNA ligase I is more similar to rat DNA ligase III than to human DNA ligase I.
authors: Istituto di Genetica, Biochimica ed Evoluzionistica, Pavia, Italy.
authors: A
authors: A
authors: Montecucco
authors: M
authors: M
authors: Lestingi
authors: J M
authors: JM
authors: Rossignol
authors: R H
authors: RH
authors: Elder
authors: G
authors: G
authors: Ciarrocchi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000037:antagonists & inhibitors*; D004214:Distamycins / Q000494:pharmacology*; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D051381:Rats; D013329:Structure-Activity Relationship; D029867:Xenopus Proteins
chemical_list: D000903:Antibiotics, Antineoplastic; D004214:Distamycins; C000607892:LIG1 protein, human; C000607895:Lig1 protein, rat; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human