Skip Navigation



Glycobiology Advance Access published online on October 11, 2007
Glycobiology, doi:10.1093/glycob/cwm105
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
17/12/1357    most recent
cwm105v1
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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Noach, N.
Right arrow Articles by Priel, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Noach, N.
Right arrow Articles by Priel, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Modification of topoisomerase I activity by glucose and by O-GlcNAcylation of the enzyme protein

Noa Noach, Yael Segev, Itzhak Levi, Shraga Segal and Esther Priel#

The Shraga Segal Dept. of Microbiology & Immunology, BGU Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, 84105, Israel.

# Corresponding author: Priel Esther, The Shraga Segal Dept. of Microbiology & Immunology, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel 84105. Tel: 972–8-6479537, Fax: 972–8-6479579, E-mail: priel{at}bgu.ac.il

Received on May 29, 2007; accepted on September 24, 2007

The regulation of topoisomerase I (topo I) activity is of prime importance for gene expression. It participates in DNA replication, transcription, recombination and DNA repair, and serves as a target for anti-cancer drugs. Many proteins and enzymes are modified by O-linked ß-N-acetylglucoseamine (O-GlcNAc) which exerts profound effects on their function. However, the modification of topo I by O-GlcNAc and the effect on its activity has not been previously reported. Here we show that topo I protein is modified by O-GlcNAc in vitro, in the porcine proximal tubular epithelial cell line (LLPCK-1), and in vivo in the mouse kidney. The level of O-GlcNAcylation of topo I protein correlates well with the enzyme activity namely, a decrease in O-GlcNac results in a reduction in topo I activity, and vice versa.

O-GlcNac transferase (OGT) was co-precipitated with topo I protein, suggesting a possible interaction between both enzymes. In addition, treatment of cells with glucosamine increased topo I activity and O-GlcNAcylation. The results of this study provide a novel mechanism for the regulation of topo I activity. Topo I is important for DNA transcription, therefore its regulation by GlcNacylation contribute to the mechanism by which glucose level affects gene expression and may pave the way to the development of new drugs which could control topo I activity.

Key words: DNA relaxation / Glucose / O-GlcNac / OGT / topoisomerase I


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




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.