The mechanism of DNA breakage by phleomycin in vitro. | Zendy

M.J. Sleigh | Zendy

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The mechanism of DNA breakage by phleomycin in vitro.

Author(s) -

M.J. Sleigh

Publication year - 1976

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/3.4.891

Subject(s) - dna , dithiothreitol , hydrogen peroxide , breakage , biology , in vitro , oxygen , biochemistry , dna damage , dna synthesis , biophysics , chemistry , enzyme , organic chemistry , materials science , composite material

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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