HUMAN DNA TOPOISOMERASES II-ALPHA AND II-BETA CAN FUNCTIONALLY SUBSTITUTE FOR YEAST TOP2 IN CHROMOSOME SEGREGATION AND RECOMBINATION

The ability of the human DNA topoisomerase II alpha and II beta isozym es to complement functional defects conferred by conditional top2 muta tions in Saccharomyces cerevisiae has been investigated. At the restri ctive temperature, top2 strains show multiple abnormalities, including an inability to complete mitotic and meiotic division owing to a defe ct in chromosome segregation, and hyper-recombination within the repet itive rDNA gene cluster. We show that the human topoisomerases II alph a and II beta can each support both vegetative growth and the producti on of viable spores in a top2-4 mutant at the restrictive temperature. Similarly, both human isozymes can rescue a strain carrying a top2 ge ne disruption, and suppress hyper-recombination within the rDNA gene c luster. We conclude that the human topoisomerase II alpha and II beta isozymes are functionally interchangeable with yeast topoisomerase II and suggest that any isozyme-specific roles in human cells are likely to be dependent upon factors other than inherent differences in cataly tic ability between the alpha and beta isozymes.