Excision of products of oxidative DNA base damage by human NTH1 protein

被引：92
作者：
Dizdaroglu, M [1 ]
Karahalil, B
Sentürker, S
Buckley, TJ
Roldán-Arjona, T
机构：
[1] Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA
[2] Gazi Univ, Fac Pharm, Dept Toxicol, Ankara, Turkey
[3] Univ Cordoba, Fac Ciencias, Dept Genet, E-14004 Cordoba, Spain
来源：
BIOCHEMISTRY | 1999年 / 38卷 / 01期
关键词：
D O I：
10.1021/bi9819071
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：243 / 246
页数：4
相关论文
共 24 条
[11]  
GROLLMAN AP, 1995, RADIATION DAMAGE IN DNA: STRUCTURE/FUNCTION RELATIONSHIPS AT EARLY TIMES, P293
[12]  
Gutfreund H., 1972, ENZYMES PHYSICAL PRI, P116
[13]   Multiply damaged sites in DNA:: interactions with Escherichia coli endonucleases III and VIII [J].
Harrison, L ;
Hatahet, Z ;
Purmal, AA ;
Wallace, SS .
NUCLEIC ACIDS RESEARCH, 1998, 26 (04) :932-941
[14]  
KAGAWA TF, 1991, J BIOL CHEM, V266, P20175
[15]   Substrate specificity of the Ogg1 protein of Saccharomyces cerevisiae:: excision of guanine lesions produced in DNA by ionizing radiation or hydrogen peroxide metal ion generated free radicals [J].
Karahalil, B ;
Girard, PM ;
Boiteux, S ;
Dizdaroglu, M .
NUCLEIC ACIDS RESEARCH, 1998, 26 (05) :1228-1232
[16]   Substrate specificity of Schizosaccharomyces pombe Nth protein for products of oxidative DNA damage [J].
Karahalil, B ;
Roldán-Arjona, T ;
Dizdaroglu, M .
BIOCHEMISTRY, 1998, 37 (02) :590-595
[17]   Kinetics of excision of purine lesions from DNA by Escherichia coli Fpg protein [J].
Karakaya, A ;
Jaruga, P ;
Bohr, VA ;
Grollman, AP ;
Dizdaroglu, M .
NUCLEIC ACIDS RESEARCH, 1997, 25 (03) :474-479
[18]   MECHANISM OF ACTION OF ESCHERICHIA-COLI ENDONUCLEASE-III [J].
KOW, YW ;
WALLACE, SS .
BIOCHEMISTRY, 1987, 26 (25) :8200-8206
[19]   Substrate specificities of the Ntg1 and Ntg2 proteins of Saccharomyces cerevisiae for oxidized DNA bases are not identical [J].
Sentürker, S ;
van der Kemp, PA ;
You, HJ ;
Doetsch, PW ;
Dizdaroglu, M ;
Boiteux, S .
NUCLEIC ACIDS RESEARCH, 1998, 26 (23) :5270-5276
[20]   MECHANISM OF MUTATION ON DNA TEMPLATES CONTAINING SYNTHETIC ABASIC SITES - STUDY WITH A DOUBLE-STRAND VECTOR [J].
TAKESHITA, M ;
EISENBERG, W .
NUCLEIC ACIDS RESEARCH, 1994, 22 (10) :1897-1902
123