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The specificity of topoisomerase-mediated DNA cleavage defines acridine-induced frameshift specificity within a hotspot in bacteriophage T4.

Publication ,  Journal Article
Masurekar, M; Kreuzer, KN; Ripley, LS
Published in: Genetics
March 1991

Acridine-induced frameshift mutations in bacteriophage T4 occur at the precise location in the DNA at which acridines stimulate DNA cleavage by the T4-encoded type II topoisomerase in vitro. The mutations are duplications or deletions that begin precisely at the broken phosphodiester bond. In vivo, acridine-induced frameshift mutagenesis is reduced nearly to background levels when the topoisomerase is genetically inactivated. These observations are consistent with a model in which cleaved DNA, induced by the topoisomerase and acridine, serves as the substrate for the production of frameshift mutations at the same site. Our model predicts that the specificity and frequency of cleavage direct the specificity and frequency of mutagenesis. This prediction was tested by examining the influence of DNA sequence changes on topoisomerase-mediated cleavage and on mutagenesis in the T4 rIIB gene. The model successfully predicted the results. When DNA sequence changes altered the position of acridine-induced, topoisomerase-mediated DNA cleavage in vitro, frameshift mutations were found at the new positions. DNA sequence changes that strongly decreased in vitro cleavage also reduced mutagenesis at that site. These results demonstrate that acridine-induced frameshift mutation specificity is directed by the characteristics of the acridine-topoisomerase reaction and do not suggest that slipped pairing in repeated sequences plays a major role in acridine-induced frameshifts in bacteriophage T4.

Duke Scholars

Published In

Genetics

DOI

ISSN

0016-6731

Publication Date

March 1991

Volume

127

Issue

3

Start / End Page

453 / 462

Location

United States

Related Subject Headings

  • T-Phages
  • Proflavine
  • Mutagenesis
  • Molecular Sequence Data
  • Frameshift Mutation
  • Developmental Biology
  • DNA, Viral
  • DNA Topoisomerases, Type II
  • DNA Repair
  • DNA Damage
 

Citation

APA
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ICMJE
MLA
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Masurekar, M., Kreuzer, K. N., & Ripley, L. S. (1991). The specificity of topoisomerase-mediated DNA cleavage defines acridine-induced frameshift specificity within a hotspot in bacteriophage T4. Genetics, 127(3), 453–462. https://doi.org/10.1093/genetics/127.3.453
Masurekar, M., K. N. Kreuzer, and L. S. Ripley. “The specificity of topoisomerase-mediated DNA cleavage defines acridine-induced frameshift specificity within a hotspot in bacteriophage T4.Genetics 127, no. 3 (March 1991): 453–62. https://doi.org/10.1093/genetics/127.3.453.
Masurekar, M., et al. “The specificity of topoisomerase-mediated DNA cleavage defines acridine-induced frameshift specificity within a hotspot in bacteriophage T4.Genetics, vol. 127, no. 3, Mar. 1991, pp. 453–62. Pubmed, doi:10.1093/genetics/127.3.453.

Published In

Genetics

DOI

ISSN

0016-6731

Publication Date

March 1991

Volume

127

Issue

3

Start / End Page

453 / 462

Location

United States

Related Subject Headings

  • T-Phages
  • Proflavine
  • Mutagenesis
  • Molecular Sequence Data
  • Frameshift Mutation
  • Developmental Biology
  • DNA, Viral
  • DNA Topoisomerases, Type II
  • DNA Repair
  • DNA Damage