A type-II DNA topoisomerase and a catenating protein from the transplantable VX2 carcinoma.
It has recently been suggested that topoisomerases could be important targets for several DNA intercalating drugs used in cancer therapy. This prompted us to purify and characterize a type II topoisomerase in a highly tumorigenic transplantable rabbit tumor isolated from a skin carcinoma associated with cottontail rabbit papillomavirus. We have found that the decatenating activity present in tumor cells was 40-100 times higher than that in the rabbit liver, while no activity could be found in skin extracts. The type II topoisomerases purified from tumor and liver cells consist of two subunits with molecular masses of about 160 kDa. The conditions of the reactions of relaxation, unknotting and decatenation catalyzed by these topoisomerases II were found to be similar to those observed with enzymes of other eukaryotic cells. In the course of the purification of the VX2 enzyme, we isolated and characterized a protein of about 30 kDa in whose presence the topoisomerase II was able to catenate very efficiently supercoiled DNA molecules. This protein has the same electrophoretic mobility as an H1-2 histone, and cross-reacts with an anti-H1 antiserum. The VX2 topoisomerase II as well as the VX2 tumor should constitute useful models for assays of antitumoral drugs.
Riou
G F
GF
Gabillot
M
M
Barrois
M
M
Breitburd
F
F
Orth
G
G
D000818:Animals; D003101:Collodion; D004250:DNA Topoisomerases, Type II / Q000302:isolation & purification* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000302:isolation & purification* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006657:Histones / Q000378:metabolism; D007120:Immunochemistry; D008099:Liver / Q000032:analysis; D009363:Neoplasm Proteins / Q000302:isolation & purification*; D009368:Neoplasm Transplantation; D027383:Papillomaviridae; D011817:Rabbits; D012878:Skin Neoplasms / Q000201:enzymology*; D014412:Tumor Virus Infections / Q000201:enzymology*
D004268:DNA-Binding Proteins; D006657:Histones; D009363:Neoplasm Proteins; D003101:Collodion; D004250:DNA Topoisomerases, Type II