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Vol. 13, Issue 1, 211-224, January 2002

Fission Yeast F-box Protein Pof3 Is Required for Genome Integrity and Telomere Function

Satoshi Katayama,^* Kenji Kitamura,^* Anna Lehmann,^* Osamu Nikaido, and Takashi Toda^*§

 ^*Laboratory of Cell Regulation, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom; and  Laboratory of Molecular and Cellular Pharmacology, Department of Pharmacology, Kanazawa University, Ishikawa 920-1192, Japan

The Skp1-Cullin-1/Cdc53-F-box protein (SCF) ubiquitin ligase plays an important role in various biological processes. In this enzyme complex, a variety of F-box proteins act as receptors that recruit substrates. We have identified a fission yeast gene encoding a novel F-box protein Pof3, which contains, in addition to the F-box, a tetratricopeptide repeat motif in its N terminus and a leucine-rich-repeat motif in the C terminus, two ubiquitous protein-protein interaction domains. Pof3 forms a complex with Skp1 and Pcu1 (fission yeast cullin-1), suggesting that Pof3 functions as an adaptor for specific substrates. In the absence of Pof3, cells exhibit a number of phenotypes reminiscent of genome integrity defects. These include G2 cell cycle delay, hypersensitivity to UV, appearance of lagging chromosomes, and a high rate of chromosome loss. pof3 deletion strains are viable because the DNA damage checkpoint is continuously activated in the mutant, and this leads to G2 cell cycle delay, thereby preventing the mutant from committing lethal mitosis. Pof3 localizes to the nucleus during the cell cycle. Molecular analysis reveals that in this mutant the telomere is substantially shortened and furthermore transcriptional silencing at the telomere is alleviated. The results highlight a role of the SCF^Pof3 ubiquitin ligase in genome integrity via maintaining chromatin structures.

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Present address: Center for Gene Science, Hiroshima University, Kagamiyama 1-4-2, Higashi-Hiroshima 739-8527 Japan.

^§ Corresponding author. E-mail address: toda{at}icrf.lif.uk.

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Molecular Biology of the Cell
Vol. 13, 211-224, January 2002
Copyright © 2002 by The American Society for Cell Biology

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