Mutational alteration of the breakage/resealing subunit of bacteriophage T4 DNA topoisomerase confers resistance to antitumor agent m-AMSA

1990 ◽  
Vol 221 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Anne C. Huff ◽  
Robert E. Ward ◽  
Kenneth N. Kreuzer
Keyword(s):  
Bacteriophage T4 ◽  
Antitumor Agent ◽  
Dna Topoisomerase

A persistent untranslated sequence within bacteriophage T4 DNA topoisomerase gene 60

Science ◽  
1988 ◽  
Vol 239 (4843) ◽  
pp. 1005-1012 ◽  
Author(s):  
W. Huang ◽  
S. Ao ◽  
S Casjens ◽  
R Orlandi ◽  
R Zeikus ◽  
...  
Keyword(s):  
Bacteriophage T4 ◽  
Dna Topoisomerase ◽  
Untranslated Sequence

Upstream stimulators for recoding

1995 ◽  
Vol 73 (11-12) ◽  
pp. 1123-1129 ◽  
Author(s):  
B. Larsen ◽  
K. Brady ◽  
J. F. Atkins ◽  
J. Peden ◽  
S. Matsufuji ◽  
...  
Keyword(s):  
Bacteriophage T4 ◽  
Gene Encoding ◽  
Dna Topoisomerase ◽  
E Coli ◽  
Optimal Spacing ◽  
A Subunit ◽  
Shine Dalgarno Sequence ◽  
Acid Domain ◽  
Frameshift Event ◽  
Amino Acid Domain

Recent progress in elucidation of 5′ stimulatory elements for translational recoding is reviewed. A 5′ Shine–Dalgarno sequence increases both +1 and −1 frameshift efficiency in several genes; examples cited include the E. coli prfB gene encoding release factor 2 and the dnaX gene encoding the γ and τ subunits of DNA polymerase III holoenzyme. The spacing between the Shine–Dalgarno sequence and the shift site is critical in both the +1 and −1 frameshift cassettes; however, the optimal spacing is quite different in the two cases. A frameshift in a mammalian chromosomal gene, ornithine decarboxylase antizyme, has recently been reported; 5′ sequences have been shown to be vital for this frameshift event. Escherichia coli bacteriophage T4 gene 60 encodes a subunit of its type II DNA topoisomerase. The mature gene 60 mRNA contains an internal 50 nucleotide region that appears to be bypassed during translation. A 16 amino acid domain of the nascent peptide is necessary for this bypass to occur.Key words: recoding, frameshifting, peptide factor, stimulatory elements.

scholarly journals Common Sites for Recombination and Cleavage Mediated by Bacteriophage T4 DNA Topoisomerase in vitro

1989 ◽  
Vol 264 (22) ◽  
pp. 12785-12790
Author(s):  
M Chiba ◽  
H Shimizu ◽  
A Fujimoto ◽  
H Nashimoto ◽  
H Ikeda
Keyword(s):  
Bacteriophage T4 ◽  
Dna Topoisomerase

Bacteriophage T4 Mutants Hypersensitive to an Antitumor Agent That Induces Topoisomerase-DNA Cleavage Complexes

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1081-1090 ◽  
Author(s):  
Denise L Woodworth ◽  
Kenneth N Kreuzer
Keyword(s):  
Dna Cleavage ◽  
Deletion Mutant ◽  
Antitumor Agents ◽  
Bacteriophage T4 ◽  
Antitumor Agent ◽  
Rnase H ◽  
Recombinational Repair ◽  
Repair Pathway ◽  
Transposon Insertion ◽  
Dna Complex

Abstract Many antitumor agents and antibiotics affect cells by interacting with type II topoisomerases, stabilizing a covalent enzyme-DNA complex. A pathway of recombination can apparently repair this DNA damage. In this study, transposon mutagenesis was used to identify possible components of the repair pathway in bacteriophage T4. Substantial increases in sensitivity to the antitumor agent m-AMSA [4′-(9-acridinylamino)methanesulfon-m-anisidide] were found with transposon insertion mutations that inactivate any of six T4-encoded proteins: UvsY (DNA synaptase accessory protein), UvsW (unknown function), Rnh (RNase H and 5′ to 3′ DNA exonuclease), α-gt (α-glucosyl transferase), gp47.1 (uncharacterized), and NrdB (β subunit of ribonucleotide reductase). The role of the rnh gene in drug sensitivity was further characterized. First, an in-frame rnh deletion mutation was constructed and analyzed, providing evidence that the absence of Rnh protein causes hypersensitivity to m-AMSA. Second, the m-AMSA sensitivity of the rnh-deletion mutant was shown to require a drug-sensitive T4 topoisomerase. Third, analysis of double mutants suggested that uvsW and rnh mutations impair a common step in the recombinational repair pathway for m-AMSA-induced damage. Finally, the rnh-deletion mutant was found to be hypersensitive to UV, implicating Rnh in recombinational repair of UV-induced damage.

Induction of mammalian DNA topoisomerase I and II mediated DNA cleavage by saintopin, a new antitumor agent from fungus

Biochemistry ◽  
1991 ◽  
Vol 30 (24) ◽  
pp. 5838-5845 ◽  
Author(s):  
Yoshinori Yamashita ◽  
Shozou Kawada ◽  
Noboru Fujii ◽  
Hirofumi Nakano
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase I ◽  
Antitumor Agent ◽  
Dna Topoisomerase I ◽  
Dna Topoisomerase

scholarly journals Repair of Topoisomerase-Mediated DNA Damage in Bacteriophage T4

Genetics ◽  
2001 ◽  
Vol 158 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Bradley A Stohr ◽  
Kenneth N Kreuzer
Keyword(s):  
Dna Damage ◽  
Cleavage Site ◽  
Bacterial Infections ◽  
Bacteriophage T4 ◽  
Antitumor Agent ◽  
Recombinational Repair ◽  
Physical Analysis ◽  
Type Ii ◽  
Drug Concentrations

Abstract Type II topoisomerase inhibitors are used to treat both tumors and bacterial infections. These inhibitors stabilize covalent DNA-topoisomerase cleavage complexes that ultimately cause lethal DNA damage. A functional recombinational repair apparatus decreases sensitivity to these drugs, suggesting that topoisomerase-mediated DNA damage is amenable to such repair. Using a bacteriophage T4 model system, we have developed a novel in vivo plasmid-based assay that allows physical analysis of the repair products from one particular topoisomerase cleavage site. We show that the antitumor agent 4′-(9-acridinylamino)-methanesulphon-m-anisidide (m-AMSA) stabilizes the T4 type II topoisomerase at the strong topoisomerase cleavage site on the plasmid, thereby stimulating recombinational repair. The resulting m-AMSA-dependent repair products do not form in the absence of functional topoisomerase and appear at lower drug concentrations with a drug-hypersensitive topoisomerase mutant. The appearance of repair products requires that the plasmid contain a T4 origin of replication. Finally, genetic analyses demonstrate that repair product formation is absolutely dependent on genes 32 and 46, largely dependent on genes uvsX and uvsY, and only partly dependent on gene 49. Very similar genetic requirements are observed for repair of endonuclease-generated double-strand breaks, suggesting mechanistic similarity between the two repair pathways.

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