Jump to ContentJump to Main Navigation

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Tate, Jillian R. / Tsongalis, Gregory J.

12 Issues per year

IMPACT FACTOR 2014: 2.707
Rank 6 out of 30 in category Medical Laboratory Technology in the 2014 Thomson Reuters Journal Citation Report/Science Edition

SCImago Journal Rank (SJR) 2014: 0.741
Source Normalized Impact per Paper (SNIP) 2014: 1.011
Impact per Publication (IPP) 2014: 2.310



Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase

Donald D. Anderson1 / Collynn F. Woeller2 / Patrick J. Stover3

1Graduate Field of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, USA

2Graduate Field of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, USA

3Graduate Field of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, USA and Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA

Corresponding author: Patrick J. Stover, Professor and Director, Division of Nutritional Sciences, 315 Savage Hall, Ithaca, NY 14853, USA Phone: +1-607-255-9751, Fax: +1-607-255-1033,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 45, Issue 12, Pages 1760–1763, ISSN (Online) 14374331, ISSN (Print) 14346621, DOI: 10.1515/CCLM.2007.355, December 2007

Publication History

Published Online:


Background: Impairments in folate-mediated one-carbon metabolism are associated with pathologies and developmental anomalies, including cardiovascular disease, cancer, neurological disorders and neural tube defects. The mechanisms that detail the role of folate and one-carbon metabolism in these disorders remain to be established. Folate deficiency impairs folate-dependent thymidylate biosynthesis resulting in depleted dTTP levels, increased rates of uracil incorporation into DNA and genomic instability. Folate-dependent enzymes involved in the de novo thymidylate pathway include cytoplasmic serine hydroxymethyltransferase (cSHMT), thymidylate synthase (TS) and dihydrofolate reductase (DHFR). Previously, we demonstrated that cSHMT-derived folate activated one-carbon units are preferentially incorporated into thymidylate, and we provided evidence that this was achieved through modification with small ubiquitin-like modifier (SUMO) enabling SUMO-dependent nuclear localization of cSHMT during S-phase.

Methods and results: Here, we provide evidence that TS and DHFR are also substrates for UBC9-catalyzed SUMOylation in vitro by SUMO-1.

Conclusions: The SUMOylation of cSHMT, TS and DHFR provides a mechanism by which all three enzymes in the thymidylate synthesis pathway are directed and compartmentalized in the nucleus.

Clin Chem Lab Med 2007;45:1760–3.

Keywords: cytoplasmic serine hydroxymethyltransferase; dihydrofolate reductase; folate; small ubiquitin-like modifier (SUMO); thymidylate; thymidylate synthase

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Morihiko Nakamura, Natsuko Watanabe, and Kaori Notsu
Biochemical and Biophysical Research Communications, 2015
Kurt Schmidt, Bernd Kolesnik, Antonius C.F. Gorren, Ernst R. Werner, and Bernd Mayer
Biochemical Pharmacology, 2014, Volume 90, Number 3, Page 246
M. Lucock, Z. Yates, C. Martin, J.-H. Choi, L. Boyd, S. Tang, N. Naumovski, J. Furst, P. Roach, N. Jablonski, G. Chaplin, and M. Veysey
Evolution, Medicine, and Public Health, 2014, Volume 2014, Number 1, Page 69
Marco Scotti, Lorenzo Stella, Emily J. Shearer, and Patrick J. Stover
Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 2013, Volume 5, Number 3, Page 343
Magalí Sáez-Ayala, María Piedad Fernández-Pérez, María F. Montenegro, Luis Sánchez-del-Campo, Soledad Chazarra, Antonio Piñero-Madrona, Juan Cabezas-Herrera, and José Neptuno Rodríguez-López
Experimental Cell Research, 2012, Volume 318, Number 10, Page 1146
Barbara Gołos, Magdalena Dąbrowska, Elżbieta Wałajtys-Rode, Zbigniew Zieliński, Patrycja Wińska, Joanna Cieśla, Elżbieta Jagielska, Tadeusz Moczoń, and Wojciech Rode
Molecular and Biochemical Parasitology, 2012, Volume 183, Number 1, Page 63
D. D. Anderson, C. M. Quintero, and P. J. Stover
Proceedings of the National Academy of Sciences, 2011, Volume 108, Number 37, Page 15163
Zigmund Luka, Frank Moss, Lioudmila V. Loukachevitch, Darryl J. Bornhop, and Conrad Wagner
Biochemistry, 2011, Volume 50, Number 21, Page 4750
Anne S. Tibbetts and Dean R. Appling
Annual Review of Nutrition, 2010, Volume 30, Number 1, Page 57
Patrick J Stover and Amanda J MacFarlane
Nutrition Reviews, 2008, Volume 66, Page S54
Ting-Ting Yuan, Ying Huang, Ci-Xiang Zhou, Yun Yu, Li-Shun Wang, Han-Yi Zhuang, and Guo-Qiang Chen
Apoptosis, 2009, Volume 14, Number 5, Page 699
Anne Parle-McDermott, Faith Pangilinan, Kirsty K. O'Brien, James L. Mills, Alan M. Magee, James Troendle, Marie Sutton, John M. Scott, Peadar N. Kirke, Anne M. Molloy, and Lawrence C. Brody
Human Mutation, 2009, Volume 30, Number 12, Page 1650
Anna E. Beaudin and Patrick J. Stover
Birth Defects Research Part A: Clinical and Molecular Teratology, 2009, Volume 85, Number 4, Page 274

Comments (0)

Please log in or register to comment.