Termination of Deoxyribonucleic Acid in Escherichia Coli by 2',3'-dideoxyadenosine

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 1970 Aug 1

PMID 4914563

Citations 7

Authors

L Toji

S S COHEN

Affiliations

Soon will be listed here.

Abstract

2',3'-Dideoxyadenosine was previously shown to be lethal to Escherichia coli and to inhibit deoxyribonucleic acid (DNA) synthesis irreversibly in this organism. It was also shown that triphosphate of this analogue terminates DNA chains in an in vitro system. Data presented here show that the nucleoside is relatively insensitive to E. coli adenosine deaminase and is converted intracellularly into the dideoxynucleotide, including the triphosphate. Thymine nucleotide pools were not reduced in inhibited bacteria, nor did preformed DNA break down. Some adenine was liberated from the dideoxyadenosine on incubation, and the latter was incorporated into ribonucleic acid. Nevertheless, about 4,000 molecules of the dideoxynucleoside were incorporated into DNA per cell. The dideoxynucleotide occurred in DNA chains in a terminal position, liberated selectively by venom phosphodiesterase. The possible nature of the lethal event is discussed.

Citing Articles

Identification of Escherichia coli dnaE (polC) mutants with altered sensitivity to 2',3'-dideoxyadenosine.

Hiratsuka K J Bacteriol. 2000; 182(14):3942-7.

PMID: 10869071 PMC: 94578. DOI: 10.1128/JB.182.14.3942-3947.2000.

Antibacterial activity of 2',3'-dideoxyadenosine in vivo and in vitro.

Beskid G, ESKIN B, Cleeland R, Siebelist J, Cappetta A, Hill A Antimicrob Agents Chemother. 1981; 19(3):424-8.

PMID: 6972730 PMC: 181448. DOI: 10.1128/AAC.19.3.424.

Penetration of mouse fibroblasts by the 5'-phosphate of 9-beta-D-arabinofuranosyladenine and incorporation of the nucleotide into DNA.

Plunkett W, Lapi L, ORTIZ P, COHEN S Proc Natl Acad Sci U S A. 1974; 71(1):73-7.

PMID: 4359332 PMC: 387934. DOI: 10.1073/pnas.71.1.73.

Antibacterial activity and mechanism of action of 3'-azido-3'-deoxythymidine (BW A509U).

ELWELL L, FERONE R, Freeman G, Fyfe J, Hill J, Ray P Antimicrob Agents Chemother. 1987; 31(2):274-80.

PMID: 3551832 PMC: 174705. DOI: 10.1128/AAC.31.2.274.

Broad spectrum antiretroviral activity of 2',3'-dideoxynucleosides.

Dahlberg J, Mitsuya H, Blam S, Broder S, Aaronson S Proc Natl Acad Sci U S A. 1987; 84(8):2469-73.

PMID: 3470806 PMC: 304673. DOI: 10.1073/pnas.84.8.2469.

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