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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 / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2016: 3.432

CiteScore 2016: 2.21

SCImago Journal Rank (SJR) 2016: 1.000
Source Normalized Impact per Paper (SNIP) 2016: 1.112

Online
ISSN
1437-4331
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Volume 45, Issue 12 (Dec 2007)

Issues

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

Donald D. Anderson
  • 1Graduate Field of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, USA
/ Collynn F. Woeller
  • 2Graduate Field of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, USA
/ Patrick J. Stover
  • 3Graduate Field of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, USA and Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
Published Online: 2007-12-08 | DOI: https://doi.org/10.1515/CCLM.2007.355

Abstract

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

About the article

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,


Received: 2007-08-06

Accepted: 2007-10-16

Published Online: 2007-12-08

Published in Print: 2007-12-01


Citation Information: Clinical Chemical Laboratory Medicine, ISSN (Online) 14374331, ISSN (Print) 14346621, DOI: https://doi.org/10.1515/CCLM.2007.355.

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