Skip Navigation



Nucleic Acids Research Advance Access published online on May 25, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm337
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (4298K) Freely available
Right arrow Screen PDF (422K) Freely available
Right arrow Supplementary Material
Right arrowOA All Versions of this Article:
35/11/3859    most recent
gkm337v1
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 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 Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Hardeland, U.
Right arrow Articles by Schär, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hardeland, U.
Right arrow Articles by Schär, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nucleic Acid Enzymes

Cell cycle regulation as a mechanism for functional separation of the apparently redundant uracil DNA glycosylases TDG and UNG2

Ulrike Hardeland2,4, Christophe Kunz1,4, Frauke Focke1, Marta Szadkowski3 and Primo Schär1,*

1Centre for Biomedicine, DKBW, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland, 2Molecular Metabolic Control, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany and 3KuDOS Pharmaceuticals Ltd., 327 Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK

*To whom correspondence should be addressed. Tel: +41 0 61 267 0767; Fax: +41 0 61 267 3566; Email: primo.schaer{at}unibas.ch

Received March 5, 2007. Revised April 18, 2007. Accepted April 19, 2007.

Human Thymine-DNA Glycosylase (TDG) is a member of the uracil DNA glycosylase (UDG) superfamily. It excises uracil, thymine and a number of chemical base lesions when mispaired with guanine in double-stranded DNA. These activities are not unique to TDG; at least three additional proteins with similar enzymatic properties are present in mammalian cells. The successful co-evolution of these enzymes implies the existence of non-redundant biological functions that must be coordinated. Here, we report cell cycle regulation as a mechanism for the functional separation of apparently redundant DNA glycosylases. We show that cells entering S-phase eliminate TDG through the ubiquitin–proteasome system and then maintain a TDG-free condition until G2. Incomplete degradation of ectopically expressed TDG impedes S-phase progression and cell proliferation. The mode of cell cycle regulation of TDG is strictly inverse to that of UNG2, which peaks in and throughout S-phase and then declines to undetectable levels until it appears again just before the next S-phase. Thus, TDG- and UNG2-dependent base excision repair alternates throughout the cell cycle, and the ubiquitin–proteasome pathway constitutes the underlying regulatory system.

4The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


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
 Phil Trans R Soc BHome page
T. Visnes, B. Doseth, H. S. Pettersen, L. Hagen, M. M.L Sousa, M. Akbari, M. Otterlei, B. Kavli, G. Slupphaug, and H. E Krokan
Uracil in DNA and its processing by different DNA glycosylases
Phil Trans R Soc B, March 12, 2009; 364(1517): 563 - 568.
[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.