Literature DB >> 818624

The mechanism of DNA breakage by phleomycin in vitro.

M J Sleigh.   

Abstract

Phleomycin induces DNA breakage in vitro in the presence of the sulphydryl compound dithiothreitol. The reaction appears to be free radical-mediated, and requires oxygen and metal ions. Reaction rate is limited by the concentration of oxygen, which is converted to hydrogen peroxide during DNA breakage. However there is no net change in the sulphydryl compound. The proposed reaction mechanism involves metal ion/oxygen-catalysed oxidation of dithiothreitol to its free radical form, which reacts with phleomycin, leading to formation of activated phleomycin and regeneration of free sulphydryl. Free phleomycin is converted to an inactive form, but activation of phleomycin bound to DNA leads to DNA breakage.

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Year:  1976        PMID： 818624      PMCID： PMC342953          DOI： 10.1093/nar/3.4.891

Source DB:  PubMed          Journal:  Nucleic Acids Res        ISSN： 0305-1048            Impact factor:   16.971


  13 in total

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Authors:  T TAKITA
Journal:  J Antibiot (Tokyo)       Date:  1959-11       Impact factor: 2.649

2.  Tissue sulfhydryl groups.

Authors:  G L ELLMAN
Journal:  Arch Biochem Biophys       Date:  1959-05       Impact factor: 4.013

3.  Chemical protection against ionizing radiation. III. Mercaptoalkylguanidines and related isothiuronium compounds with protective activity.

Authors:  R SHAPIRA; D G DOHERTY; W T BURNETT
Journal:  Radiat Res       Date:  1957-07       Impact factor: 2.841

4.  A new antibiotic, phleomycin.

Authors:  K MAEDA; H KOSAKA; K YAGISHITA; H UMEZAWA
Journal:  J Antibiot (Tokyo)       Date:  1956-03       Impact factor: 2.649

5.  Inactivation of biologically active DNA by gamma-ray-induced superoxide radicals and their dismutation products singlet molecular oxygen and hydrogen peroxide.

Authors:  J J Van Hemmen; W J Meuling
Journal:  Biochim Biophys Acta       Date:  1975-08-21

6.  Action of bleomycin on DNA and RNA.

Authors:  W E Müller; Z Yamazaki; H J Breter; R K Zahn
Journal:  Eur J Biochem       Date:  1972-12-18

7.  Induction of local denaturation in DNA in vitro by phleomycin and caffeine.

Authors:  M J Sleigh; G W Grigg
Journal:  FEBS Lett       Date:  1974-02-01       Impact factor: 4.124

8.  Phleomycin-induced cleavage of deoxyribonucleic acid.

Authors:  R Stern; J A Rose; R M Friedman
Journal:  Biochemistry       Date:  1974-01-15       Impact factor: 3.162

9.  Effects of reducing and oxidizing agents on the action of bleomycin.

Authors:  T Onishi; H Iwata; Y Takagi
Journal:  J Biochem       Date:  1975-04       Impact factor: 3.387

10.  On the mechanism of action of bleomycin. Strand scission of DNA caused by bleomycin and its binding to DNA in vitro.

Authors:  H Suzuki; K Nagai; E Akutsu; H Yamaki; N Tanaka
Journal:  J Antibiot (Tokyo)       Date:  1970-10       Impact factor: 2.649
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9.  Nuclear Deformation Causes DNA Damage by Increasing Replication Stress.

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10.  Cdc28/Cdk1 positively and negatively affects genome stability in S. cerevisiae.

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