The influence of DNA gyrase on the transcription of linear DNA in vitro

Shmerling, Zh.G.; Gragerov, Alexander

doi:10.1016/0014-5793(82)80909-5

Cited by 2 publications

(1 citation statement)

References 7 publications

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“…Expression of late, but not of early, genes of the linear DNA of the phage T7 is in vivo efficiently suppressed after inhibition of gyrase (DE WYNGERT and HINKLE 1979). Stimulation of transcription with E. coli RNA polymerase by gyrase has also been observed in vitro with linear phage ADNA, but not with linear phage T7 DNA (SHMERLING and GRAGEROV 1982). Whether DNAspecific local supercoiling is involved, as it was suggested by the authors, is not known.…”

Section: Prokaryotic Topoisomerasesmentioning

confidence: 69%

DNA Topoisomerases: Enzymes That Control DNA Conformation

Vosberg

1985

Current Topics in Microbiology and Immunology

234

166

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Section: Prokaryotic Topoisomerasesmentioning

confidence: 69%

DNA Topoisomerases: Enzymes That Control DNA Conformation

Vosberg

1985

Current Topics in Microbiology and Immunology

234

166

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A Mutation in Human Topoisomerase II α Whose Expression Is Lethal in DNA Repair-deficient Yeast Cells

Walker

Nitiss

Jensen

et al. 2004

Journal of Biological Chemistry

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Type II DNA topoisomerases are ATP-dependent enzymes that catalyze alterations in DNA topology. These enzymes are important targets of a variety of anti-bacterial and anti-cancer agents. We identified a mutation in human topoisomerase II ␣, changing aspartic acid 48 to asparagine, that has the unique property of failing to transform yeast cells deficient in recombinational repair. In repair-proficient yeast strains, the Asp-48 3 Asn mutant can be expressed and complements a temperature-sensitive top2 mutation. Purified Asp-48 3 Asn Top2␣ has relaxation and decatenation activity similar to the wild type enzyme, but the purified protein exhibits several biochemical alterations compared with the wild type enzyme. The mutant enzyme binds both covalently closed and linear DNA with greater avidity than the wild type enzyme. hTop2␣(Asp-48 3 Asn) also exhibited elevated levels of drug-independent cleavage compared with the wild type enzyme. The enzyme did not show altered sensitivity to bisdioxopiperazines nor did it form stable closed clamps in the absence of ATP, although the enzyme did form elevated levels of closed clamps in the presence of a non-hydrolyzable ATP analog compared with the wild type enzyme. We suggest that the lethality exhibited by the mutant is likely because of its enhanced drug-independent cleavage, and we propose that alterations in the ATP binding domain of the enzyme are capable of altering the interactions of the enzyme with DNA. This mutant enzyme also serves as a new model for understanding the action of drugs targeting topoisomerase II.Type II topoisomerases catalyze changes in DNA topology in an ATP-dependent mechanism (for recent reviews see Refs. 1 and 2). Changes in DNA topology require cleavage of the DNA backbone. For eukaryotic type II topoisomerases, DNA cleavage results from a transesterification reaction between phosphates in the DNA backbone and catalytic tyrosines from each of the two identical subunits of the enzyme, resulting in a protein-bridged DNA double-strand break. ATP binding and hydrolysis are required for the enzyme to carry out catalytic changes in DNA topology, although the high energy cofactor does not play a direct role in the breakage/reunion reaction of the enzyme. Current models suggest that ATP hydrolysis is required for regeneration of the enzyme to complete the catalytic cycle (3, 4), although it has been suggested that ATP hydrolysis may also accelerate strand transfer reactions (5). In addition to an absolute requirement for type II topoisomerase activity in processes such as chromosome segregation (6, 7), these enzymes are targeted by a number of antibacterial and anticancer agents in widespread clinical use. Drugs targeting DNA topoisomerases principally act by increasing the levels of the covalent complex that is an intermediate of the enzyme reaction (reviewed in Refs. 2, 8, and 9).The overall domain organization of prokaryotic and eukaryotic type II topoisomerases is similar, although the eukaryotic enzyme is a homodimer, and the prokaryotic enzymes a...

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The influence of DNA gyrase on the transcription of linear DNA in vitro

Cited by 2 publications

References 7 publications

DNA Topoisomerases: Enzymes That Control DNA Conformation

DNA Topoisomerases: Enzymes That Control DNA Conformation

A Mutation in Human Topoisomerase II α Whose Expression Is Lethal in DNA Repair-deficient Yeast Cells

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