Structure and mechanism of hydroxyl radical-induced formation of a DNA-protein cross-link involving thymine and lysine in nucleohistone

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · Cancer Research; (USA)

OSTI ID:5600873

Dizdaroglu, M; Gajewski, E ^[1]

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1. National Institute of Standards and Technology, Gaithersburg, MD (USA)

Hydroxyl radical-induced formation of a DNA-protein cross-link involving thymine and lysine in calf thymus nucleohistone in vitro is reported. Basic amino acids such as lysine constitute a very high proportion of the amino acids of histones, and help histones to bind to DNA in chromatin. For this reason, basic amino acids are likely to participate in DNA-protein cross-linking. For identification of the thymine-lysine cross-link in nucleohistone, hydroxyl radical-induced cross-linking of thymine to lysine was investigated first using a model system, i.e., an aqueous mixture of thymine and lysine. Hydroxyl radicals were generated by exposure of this mixture to ionizing radiation after N{sub 2}O saturation. The technique of gas chromatography-mass spectrometry was used to analyze the samples for possible cross-links. One thymine-lysine cross-link was found and its structure was elucidated. Using gas chromatography-mass spectrometry with selected-ion monitoring, this thymine-lysine cross-link was identified in acidic hydrolysates of calf thymus nucleohistone gamma-irradiated in N{sub 2}O-saturated aqueous solution. The yield of this DNA-protein cross-link was also measured and found to be a linear function of radiation dose between 15 and 200 Gy. This yield amounted to 0.0085 mumol/J. Possible mechanisms for the formation of this DNA-protein cross-link in nucleohistone were proposed.

• OSTI ID: 5600873
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 49:13; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMALS
AZINES
BIOSYNTHESIS
CARBOXYLIC ACIDS
CATTLE
CHEMICAL RADIATION EFFECTS
CHEMICAL REACTIONS
CHEMISTRY
CHROMATOGRAPHY
CROSS-LINKING
DNA
DOMESTIC ANIMALS
ELECTROMAGNETIC RADIATION
GAMMA RADIATION
GAS CHROMATOGRAPHY
HETEROCYCLIC COMPOUNDS
HISTONES
HYDROGEN COMPOUNDS
HYDROXIDES
HYDROXY COMPOUNDS
HYDROXYL RADICALS
IN VITRO
IONIZING RADIATIONS
LYSINE
MAMMALS
MASS SPECTROSCOPY
MOLECULAR STRUCTURE
NUCLEIC ACIDS
NUCLEOPROTEINS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXYGEN COMPOUNDS
POLYMERIZATION
PROTEINS
PYRIMIDINES
RADIATION CHEMISTRY
RADIATION EFFECTS
RADIATIONS
RADICALS
RUMINANTS
SEPARATION PROCESSES
SPECTROSCOPY
SYNTHESIS
THYMINE
URACILS
VERTEBRATES