This Article Full Text Full Text (PDF) Supplemental material Other Versions of this Article: MCB.00323-06v1 27/1/229    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mohan, R. D. Articles by Tini, M. Search for Related Content PubMed PubMed Citation Articles by Mohan, R. D. Articles by Tini, M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2007, p. 229-243, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.00323-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

SUMO-1-Dependent Allosteric Regulation of Thymine DNA Glycosylase Alters Subnuclear Localization and CBP/p300 Recruitment ^,

Ryan D. Mohan,^1, Anita Rao,^1, Jason Gagliardi,^2, and Marc Tini^1,2*

Departments of Physiology and Pharmacology,¹ Department of Microbiology and Immunology, Siebens-Drake Medical Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6G 2V4²

Received 21 February 2006/ Returned for modification 26 April 2006/ Accepted 10 October 2006

Previous studies have demonstrated that the base excision repair enzyme thymine DNA glycosylase (TDG) mediates recruitment of histone acetyltransferases CREB-binding protein (CBP) and p300 to DNA, suggesting a plausible role for these factors in TDG-mediated repair. Furthermore, TDG was found to potentiate CBP/p300-dependent transcription and serve as a substrate for CBP/p300 acetylation. Here, we show that the small ubiquitin-like modifier 1 (SUMO-1) protein binding activity of TDG is essential for activation of CBP and localization to promyelocytic leukemia protein oncogenic domains (PODs). SUMO-1 binding is mediated by two distinct amino- and carboxy-terminal motifs (residues 144 to 148 and 319 to 322) that are negatively regulated by DNA binding via an amino-terminal hydrophilic region (residues 1 to 121). TDG is also posttranslationally modified by covalent conjugation of SUMO-1 (sumoylation) to lysine 341. Interestingly, we found that sumoylation of TDG blocks interaction with CBP and prevents TDG acetylation in vitro. Furthermore, sumoylation effectively abrogates intermolecular SUMO-1 binding and a sumoylation-deficient mutant accumulates in PODs, suggesting that sumoylation negatively regulates translocation to these nuclear structures. These findings suggest that TDG sumoylation promotes intramolecular interactions with amino- and carboxy-terminal SUMO-1 binding motifs that dramatically alter the biochemical properties and subcellular localization of TDG.

Published ahead of print on 23 October 2006.

Supplemental material for this article may be found at http://mcb.asm.org/.

R.D.M., A.R., and J.G. contributed equally to the manuscript.

This article has been cited by other articles:

• Lee, J., Lee, Y., Lee, M. J., Park, E., Kang, S. H., Chung, C. H., Lee, K. H., Kim, K. (2008). Dual Modification of BMAL1 by SUMO2/3 and Ubiquitin Promotes Circadian Activation of the CLOCK/BMAL1 Complex. Mol. Cell. Biol. 28: 6056-6065 [Abstract] [Full Text]  
• Hardeland, U., Kunz, C., Focke, F., Szadkowski, M., Schar, P. (2007). Cell cycle regulation as a mechanism for functional separation of the apparently redundant uracil DNA glycosylases TDG and UNG2. Nucleic Acids Res 35: 3859-3867 [Abstract] [Full Text]