Mitochondrial DNA topoisomerase I of Saccharomyces cerevisiae.
A mitochondrial DNA topoisomerase (type I, ATP-independent) can be biochemically distinguished from the nuclear enzyme DNA topoisomerase I. This conclusion is based on the subcellular localization of the mitochondrial enzyme, its optimal reaction conditions and sensitivity to enzyme inhibitors. Unlike its nuclear counterpart, the mitochondrial DNA topoisomerase exhibits an absolute requirement for a divalent cation (Mg2+ and Ca2+ work equally well in vitro). In addition, it is slightly more sensitive to monovalent salts, with optimal activity obtained in 50-100 mM KCl. The mitochondrial enzyme is equally active at pH 7.5 or pH 9.5, but unlike its nuclear equivalent, is inactivated at higher pH values. The mitochondrial DNA topoisomerase is sensitive to coumermycin, berenil, camptothecin and 2,2,5,5-tetramethyl-4-imidazolidinone, a chemical that has no inhibitory effect on DNA topoisomerase I. Immunoblotting studies show that mitochondrial DNA topoisomerase activity is associated with a polypeptide (M(r) approximately 79,000) that cross-reacts with the antiserum against DNA topoisomerase I. Thus, the mitochondrial DNA topoisomerase may be derived by the differential expression of the DNA topoisomerase I gene or from the expression of a gene that is homologous to the DNA topoisomerase I gene.
Tua
A
A
Department of Chemistry, Auburn University, AL 36849-5312, USA.
Wang
J
J
Kulpa
V
V
Wernette
C M
CM
D049933:Aminocoumarins; D002166:Camptothecin / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology; D004264:DNA Topoisomerases, Type I / Q000032:analysis* / Q000302:isolation & purification; D004133:Diminazene / Q000031:analogs & derivatives / Q000494:pharmacology; D004202:Disinfectants / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D059004:Topoisomerase I Inhibitors
C108762:2,2,5,5-tetramethyl-4-imidazolidinone; D049933:Aminocoumarins; D003374:Coumarins; D004202:Disinfectants; D007093:Imidazoles; D059004:Topoisomerase I Inhibitors; C069218:1,3-dichloro-4,4,5,5-tetramethyl-2-imidazolidinone; D004264:DNA Topoisomerases, Type I; C003915:diminazene aceturate; C004628:coumermycin; D002166:Camptothecin; D004133:Diminazene