Excision of Products of Oxidative DNA Base Damage by Human NTH1 Protein

A functional human homologue of Escherichia coli endonuclease III (Nth-Eco protein) has recently been cloned and characterized [Aspinwall, R., Rothwell, D. G., Roldan-Arjona, T., Anselmino, C., Ward, C. J., Cheadle, J. P., Sampson, J. R., Lindahl, T., Harris, P. C., and Hickson, I. D. (1997) Proc. N...

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Published in:Biochemistry (Easton) 1999-01, Vol.38 (1), p.243-246
Main Authors: Dizdaroglu, Miral, Karahalil, Bensu, Sentürker, Sema, Buckley, Thomas J, Roldán-Arjona, Teresa
Format: Article
Language:English
Subjects:
Barbiturates - metabolism
Cytosine - analogs & derivatives
Cytosine - metabolism
Deoxyribonuclease (Pyrimidine Dimer)
DNA - chemistry
DNA - drug effects
DNA - metabolism
DNA Damage - drug effects
DNA Repair
Endodeoxyribonucleases - chemistry
Endodeoxyribonucleases - metabolism
Endodeoxyribonucleases - pharmacology
Escherichia coli - enzymology
Escherichia coli Proteins
Humans
Kinetics
Oxidation-Reduction
Substrate Specificity
Thymine - analogs & derivatives
Thymine - metabolism
Uracil - analogs & derivatives
Uracil - metabolism
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Summary:A functional human homologue of Escherichia coli endonuclease III (Nth-Eco protein) has recently been cloned and characterized [Aspinwall, R., Rothwell, D. G., Roldan-Arjona, T., Anselmino, C., Ward, C. J., Cheadle, J. P., Sampson, J. R., Lindahl, T., Harris, P. C., and Hickson, I. D. (1997) Proc. Natl. Acad. Sci. U.S.A., 94, 109−114]. This enzyme, designated hNTH1 protein, shares an extensive sequence similarity with Nth-Eco protein and a related enzyme from Schizosaccharomyces pombe (Nth-Spo protein). We investigated the substrate specificity of this human enzyme for oxidative DNA base damage, using the technique of gas chromatography/isotope-dilution mass spectrometry. Four different DNA substrates damaged by various free radical-generating systems were used. 5-Hydroxycytosine, thymine glycol, 5-hydroxy-6-hydrothymine, 5,6-dihydroxycytosine, and 5-hydroxyuracil were substrates of hNTH1 protein among 17 lesions found in DNA substrates. The substrate specificity and excision kinetics of the human enzyme were found to be significantly different from those of Nth-Spo and Nth-Eco proteins.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi9819071