Nucleic Acids Research, 2001, Vol. 29, No. 9 1975-1981
© 2001 Oxford University Press
Escherichia coli Nth and human hNTH1 DNA glycosylases are involved in removal of 8-oxoguanine from 8-oxoguanine/guanine mispairs in DNA
Laboratory of Radiation Biology, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan and 1Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai 980-8575, Japan
The spectrum of DNA damage caused by reactive oxygen species includes a wide variety of modifications of purine and pyrimidine bases. Among these modified bases, 7,8-dihydro-8-oxoguanine (8-oxoG) is an important mutagenic lesion. Base excision repair is a critical mechanism for preventing mutations by removing the oxidative lesion from the DNA. That the spontaneous mutation frequency of the Escherichia coli mutT mutant is much higher than that of the mutM or mutY mutant indicates a significant potential for mutation due to 8-oxoG incorporation opposite A and G during DNA replication. In fact, the removal of A and G in such a situation by MutY protein would fix rather than prevent mutation. This suggests the need for differential removal of 8-oxoG when incorporated into DNA, versus being generated in situ. In this study we demonstrate that E.coli Nth protein (endonuclease III) has an 8-oxoG DNA glycosylase/AP lyase activity which removes 8-oxoG preferentially from 8-oxoG/G mispairs. The MutM and Nei proteins are also capable of removing 8-oxoG from mispairs. The frequency of spontaneous G:C
C:G transversions was significantly increased in E.coli CC103mutMnthnei mutants compared with wild-type, mutM, nth, nei, mutMnei, mutMnth and nthnei strains. From these results it is concluded that Nth protein, together with the MutM and Nei proteins, is involved in the repair of 8-oxoG when it is incorporated opposite G. Furthermore, we found that human hNTH1 protein, a homolog of E.coli Nth protein, has similar DNA glycosylase/AP lyase activity that removes 8-oxoG from 8-oxoG/G mispairs.
* To whom correspondence should be addressed. Tel: +81 75 753 4097; Fax: +81 75 753 4087; Email: yonei{at}kingyo.zool.kyoto-u.ac.jp
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A R Dallosso, S Dolwani, N Jones, S Jones, J Colley, J Maynard, S Idziaszczyk, V Humphreys, J Arnold, A Donaldson, et al. Inherited predisposition to colorectal adenomas caused by multiple rare alleles of MUTYH but not OGG1, NUDT1, NTH1 or NEIL 1, 2 or 3 Gut, September 1, 2008; 57(9): 1252 - 1255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Saumaa, A. Tover, M. Tark, R. Tegova, and M. Kivisaar Oxidative DNA Damage Defense Systems in Avoidance of Stationary-Phase Mutagenesis in Pseudomonas putida J. Bacteriol., August 1, 2007; 189(15): 5504 - 5514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Shikazono, C. Pearson, P. O'Neill, and J. Thacker The roles of specific glycosylases in determining the mutagenic consequences of clustered DNA base damage Nucleic Acids Res., August 7, 2006; 34(13): 3722 - 3730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Hill and M. K. Evans Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase Nucleic Acids Res., March 20, 2006; 34(5): 1620 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Doi, A. Katafuchi, Y. Fujiwara, K. Hitomi, J. A. Tainer, H. Ide, and S. Iwai Synthesis and characterization of oligonucleotides containing 2'-fluorinated thymidine glycol as inhibitors of the endonuclease III reaction Nucleic Acids Res., March 17, 2006; 34(5): 1540 - 1551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jensen, G. Calvayrac, B. Karahalil, V. A. Bohr, and T. Stevnsner Mammalian 8-Oxoguanine DNA Glycosylase 1 Incises 8-Oxoadenine Opposite Cytosine in Nuclei and Mitochondria, while a Different Glycosylase Incises 8-Oxoadenine Opposite Guanine in Nuclei J. Biol. Chem., May 23, 2003; 278(21): 19541 - 19548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Chung, E. K. Im, H.-Y. Park, J. H. Kwon, S. Lee, J. Oh, K.-C. Hwang, J. H. Lee, and Y. Jang A novel uracil-DNA glycosylase family related to the helix-hairpin-helix DNA glycosylase superfamily Nucleic Acids Res., April 15, 2003; 31(8): 2045 - 2055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hori, S. Yonei, H. Sugiyama, K. Kino, K. Yamamoto, and Q.-M. Zhang Identification of high excision capacity for 5-hydroxymethyluracil mispaired with guanine in DNA of Escherichia coli MutM, Nei and Nth DNA glycosylases Nucleic Acids Res., February 15, 2003; 31(4): 1191 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Miyabe, Q.-M. Zhang, K. Kino, H. Sugiyama, M. Takao, A. Yasui, and S. Yonei Identification of 5-formyluracil DNA glycosylase activity of human hNTH1 protein Nucleic Acids Res., August 1, 2002; 30(15): 3443 - 3448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Hazra, T. Izumi, I. Boldogh, B. Imhoff, Y. W. Kow, P. Jaruga, M. Dizdaroglu, and S. Mitra From the Cover: Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA PNAS, March 19, 2002; 99(6): 3523 - 3528. [Abstract] [Full Text] [PDF]
|
|