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Eukaryotic Cell, April 2004, p. 406-412, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.406-412.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cell Division Defects of Schizosaccharomyces pombe liz1^– Mutants Are Caused by Defects in Pantothenate Uptake

Jürgen Stolz,^1,* Thomas Caspari,^2,, Antony M. Carr,² and Norbert Sauer³

Department of Cell Biology and Plant Physiology, Universität Regensburg, D-93040 Regensburg,¹ Department of Molecular Plant Physiology, Friedrich-Alexander Universität Erlangen-Nürnberg, D-91058 Erlangen, Germany,³ Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, United Kingdom²

Received 26 October 2003/ Accepted 5 February 2004

The liz1⁺ gene of the fission yeast Schizosaccharomyces pombe was previously identified by complementation of a mutation that causes abnormal mitosis when ribonucleotide reductase is inhibited. Liz1 has similarity to transport proteins from Saccharomyces cerevisiae, but the potential substrate and its connection to the cell division cycle remain elusive. We report here that liz1⁺ encodes a plasma membrane-localized active transport protein for the vitamin pantothenate, the precursor of coenzyme A (CoA). Liz1 is required for pantothenate uptake at low extracellular concentrations. A lack of pantothenate uptake results in three phenotypes: (i) slow growth, (ii) delayed septation, and (iii) aberrant mitosis in the presence of hydroxyurea (HU). All three phenotypes are suppressed by high extracellular concentrations of pantothenate, where pantothenate uptake occurs by passive diffusion. liz1 mutants are viable because they can synthesize pantothenate from uracil as an endogenous source. The use of uracil for both pantothenate biosynthesis and deoxyribonucleotide generation provides an explanation for the aberrant mitosis in the presence of HU. HU blocks ribonucleotide reductase, and we propose that the accumulation of ribonucleotides reduces uracil biosynthesis by feedback inhibition of aspartate transcarbamoylase. Thus, the addition of HU to liz1 mutants results in a shortage of pantothenate. Because liz1 mutants show striking similarities to mutants with defects in fatty acid biosynthesis, we propose that the shortage of pantothenate compromises fatty acid synthesis, resulting in slow growth and mitotic defects.

J.S. and T.C. made equal contributions to this work.

Present address: Pieris Proteolab AG, D-85354 Freising-Weihenstephan, Germany.

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