PMID: 2109323Apr 1, 1990Paper

Diphtheria toxin and its ADP-ribosyltransferase-defective homologue CRM197 possess deoxyribonuclease activity

Proceedings of the National Academy of Sciences of the United States of America
C BruceB J Wisnieski

Abstract

The cytotoxic mechanism of diphtheria toxin (DTx) is associated with its ability to inhibit protein synthesis by ADP-ribosylation of elongation factor 2. Although DTx intoxication leads to internucleosomal DNA cleavage and cell lysis, these events do not occur when protein synthesis is inhibited by alternative treatments (e.g., cycloheximide). Here we show that endonucleolytic degradation of DNA is an intrinsic activity of DTx and also of the crossreactive mutant protein CRM197. Assays using DNA-impregnated gels as well as linear and supercoiled DNA in solution revealed not only that CRM197 has nuclease activity but also that its specific activity is actually significantly greater than that of the wild-type molecule. Since CRM197 contains a single amino acid substitution that renders it incapable of ADP-ribosylation, we propose that the active sites for ADP-ribosyltransferase and nuclease activities are distinct.

References

May 15, 1977·Analytical Biochemistry·A L Rosenthal, S A Lacks
Mar 28, 1977·Biochimica Et Biophysica Acta·A Michel, J Dirkx
May 3, 1988·Biochemistry·J M Zhao, E London
Jan 1, 1986·Annual Review of Biochemistry·D M Neville, T H Hudson
Apr 5, 1985·Biochimica Et Biophysica Acta·C M Collins, R J Collier
Jun 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S F Carroll, R J Collier
Jul 1, 1983·Analytical Biochemistry·A P Feinberg, B Vogelstein
Jun 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·L S Zalman, B J Wisnieski
Jan 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·M YamaizumiY Okada

❮ Previous
Next ❯

Citations

Sep 6, 2011·Journal of Biotechnology·Alessandra StefanAlejandro Hochkoeppler
Mar 30, 2016·Applied Microbiology and Biotechnology·Pornpimol MahamadWatanalai Panbangred
Dec 6, 2011·Cellular & Molecular Biology Letters·Başak VarolEngin Bermek
Nov 12, 2016·Toxins·Marta BorowiecKrzysztof Ginalski
Apr 28, 2021·Biochemical and Biophysical Research Communications·Maria Laura BelloneAlejandro Hochkoeppler
Mar 1, 1992·Journal of Bacteriology·S L LessnickB J Wisnieski
Feb 1, 2005·Biochimica Et Biophysica Acta·Jason W LeeBernadine J Wisnieski
Aug 29, 2019·ACS Omega·Nathalie Bravo-BautistaNathan J Wymer
Nov 9, 1990·Science·B A WilsonR J Collier
Nov 9, 1990·Science·S L LessnickB J Wisnieski

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.