title: Human DNA topoisomerases II alpha and II beta can functionally substitute for yeast TOP2 in chromosome segregation and recombination.
abstract: The ability of the human DNA topoisomerase II alpha and II beta isozymes to complement functional defects conferred by conditional top2 mutations in Saccharomyces cerevisiae has been investigated. At the restrictive temperature, top2 strains show multiple abnormalities, including an inability to complete mitotic and meiotic division owing to a defect in chromosome segregation, and hyper-recombination within the repetitive rDNA gene cluster. We show that the human topoisomerases II alpha and II beta can each support both vegetative growth and the production of viable spores in a top2-4 mutant at the restrictive temperature. Similarly, both human isozymes can rescue a strain carrying a top2 gene disruption, and suppress hyper-recombination within the rDNA gene cluster. 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 catalytic ability between the alpha and beta isozymes.
authors.affiliation: Department of Molecular Biology, University of Aarhus, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Jensen
authors.forename: C S
authors.initials: CS
authors.lastname: Redwood
authors.forename: J R
authors.initials: JR
authors.lastname: Jenkins
authors.forename: A H
authors.initials: AH
authors.lastname: Andersen
authors.forename: I D
authors.initials: ID
authors.lastname: Hickson
mesh_terms: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015870:Gene Expression; D005816:Genetic Complementation Test; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis / Q000235:genetics; D009154:Mutation; D000075223:Poly-ADP-Ribose Binding Proteins; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D013172:Spores, Fungal / Q000502:physiology; D013696:Temperature; D014170:Transformation, Genetic
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human