Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (315K) 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 (6)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Friedrich-Heineken, E.
Right arrow Articles by Hübscher, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Friedrich-Heineken, E.
Right arrow Articles by Hübscher, U.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 6 May 2004

Nucleic Acids Research, 2004, Vol. 32, No. 8 2520-2528
© 2004 Oxford University Press

The Fen1 extrahelical 3'-flap pocket is conserved from archaea to human and regulates DNA substrate specificity

Erica Friedrich-Heineken and Ulrich Hübscher*

Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH 8057 Zürich, Switzerland

*To whom correspondence should be addressed. Tel: +41 1 6355472; Fax: +41 1 6356840; Email: hubscher{at}vetbio.unizh.ch

Received February 20, 2004; Revised March 24, 2004; Accepted April 12, 2004

Fen1 is a key enzyme for the maintenance of genetic stability in archaea and eukaryotes and is classified as a tumor suppressor. Very recent structural data obtained from Archaeoglobus fulgidus Fen1 suggest that an extrahelical 3'-flap pocket is responsible for substrate specificity, by binding to the unpaired 3'-flap and by opening and kinking the DNA. Since the extrahelical 3'-flap pocket in archaeal Fen1 contains seven amino acids that are conserved to a great extent in human Fen1, we have mutated the four conserved or all seven amino acids in the human Fen1 extrahelical 3'-flap pocket to alanine. Our data suggest that the human extrahelical 3'-flap pocket mutants have lost substrate specificity to the double-flap DNA. Moreover, loss of high affinity for the unpaired 3'-flap suggests that the extrahelical 3'-flap pocket is essential for recognition and processing of the ‘physiological’ template. Human PCNA could stimulate the human Fen1 extrahelical 3'-flap pocket mutants but not restore their specificity. Thus the substrate specificity of Fen1 has been functionally conserved over a billion years from archaea to human.


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
 Nucleic Acids ResHome page
M. Hohl, I. Dunand-Sauthier, L. Staresincic, P. Jaquier-Gubler, F. Thorel, M. Modesti, S. G. Clarkson, and O. D. Scharer
Domain swapping between FEN-1 and XPG defines regions in XPG that mediate nucleotide excision repair activity and substrate specificity
Nucleic Acids Res., May 14, 2007; 35(9): 3053 - 3063.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
R. Liu, J. Qiu, L. D. Finger, L. Zheng, and B. Shen
The DNA-protein interaction modes of FEN-1 with gap substrates and their implication in preventing duplication mutations.
Nucleic Acids Res., January 1, 2006; 34(6): 1772 - 1784.
[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.