Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (151K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (14)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Miyabe, I.
Right arrow Articles by Yonei, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miyabe, I.
Right arrow Articles by Yonei, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2002, Vol. 30, No. 15 3443-3448
© 2002 Oxford University Press

Identification of 5-formyluracil DNA glycosylase activity of human hNTH1 protein

Izumi Miyabe, Qiu-Mei Zhang, Katsuhito Kino1, Hiroshi Sugiyama1, Masashi Takao2, Akira Yasui2 and Shuji Yonei*

Laboratory of Radiation Biology, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan, 1 Institute for Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan and 2 Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai 980-8575, Japan

*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

5-Formyluracil (5-foU) is a potentially mutagenic lesion of thymine produced in DNA by ionizing radiation and various chemical oxidants. The elucidation of repair mechanisms for 5-foU will yield important insights into the biological consequences of the lesion. Recently, we reported that 5-foU is recognized and removed from DNA by Escherichia coli enzymes Nth (endonuclease III), Nei (endonuclease VIII) and MutM (formamidopyrimidine DNA glycosylase). Human cells have been shown to have enzymatic activities that release 5-foU from X-ray-irradiated DNA, but the molecular identities of these activities are not yet known. In this study, we demonstrate that human hNTH1 (endonuclease III homolog) has a DNA glycosylase/AP lyase activity that recognizes 5-foU in DNA and removes it. hNTH1 cleaved 5-foU-containing duplex oligonucleotides via a ß-elimination reaction. It formed Schiff base intermediates with 5-foU-containing oligonucleotides. Furthermore, hNTH1 cleaved duplex oligonucleotides containing all of the 5-foU/N pairs (N = G, A, T or C). The specific activities of hNTH1 for cleavage of oligonucleotides containing 5-foU and thymine glycol were 0.011 and 0.045 nM/min/ng protein, respectively. These results indicate that hNTH1 has DNA glycosylase activity with the potential to recognize 5-foU in DNA and remove it in human cells.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
M. Goto, K. Shinmura, H. Igarashi, M. Kobayashi, H. Konno, H. Yamada, M. Iwaizumi, S. Kageyama, T. Tsuneyoshi, S. Tsugane, et al.
Altered expression of the human base excision repair gene NTH1 in gastric cancer
Carcinogenesis, August 1, 2009; 30(8): 1345 - 1352.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Q.-M. Zhang-Akiyama, H. Morinaga, M. Kikuchi, S.-I. Yonekura, H. Sugiyama, K. Yamamoto, and S. Yonei
KsgA, a 16S rRNA adenine methyltransferase, has a novel DNA glycosylase/AP lyase activity to prevent mutations in Escherichia coli
Nucleic Acids Res., April 1, 2009; 37(7): 2116 - 2125.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
G.ég. Eot-Houllier, Sév. Eon-Marchais, D. Gasparutto, and E. Sage
Processing of a complex multiply damaged DNA site by human cell extracts and purified repair proteins
Nucleic Acids Res., January 12, 2005; 33(1): 260 - 271.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
M. S. COOKE, M. D. EVANS, M. DIZDAROGLU, and J. LUNEC
Oxidative DNA damage: mechanisms, mutation, and disease
FASEB J, July 1, 2003; 17(10): 1195 - 1214.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
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]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.