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Conserved Wat1/Pop3 WD-repeat protein of fission yeast secures genome stability through microtubule integrity and may be involved in mRNA maturation

Iciar L. Ochotorena^1,*,, Dai Hirata^2,*, Kin-ichiro Kominami^1,, Judith Potashkin³, Fikret Sahin⁴, Kelly Wentz-Hunter³, Kathleen L. Gould⁵, Kazuhito Sato², Yasuko Yoshida², Leah Vardy¹ and Takashi Toda^1,¶

¹ Laboratory of Cell Regulation, Imperial Cancer Research Fund, PO Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
² Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, and `Unit Process and Combined Circuit', PRESTO, JST, Higashi-Hiroshima 739-8526, Japan
³ Department of Cellular and Molecular Pharmacology, Finch University of Health Science, The Chicago Medical School, North Chicago, IL 60064, USA
⁴ Department of Microbiology and Immunology, Finch University of Health Science, The Chicago Medical School, North Chicago, IL 60064, USA
⁵ Howard Hughes Medical Institute and Department of Cell Biology, Vanderbilt University, Nashville, TN 37232, USA
^* These authors contributed equally to this work
Present address: Nomura Research & Advisory Co. Ltd., Urbannet Otemachi Building 2-2-2, Otemachi, Chiyoda-ku, Tokyo 100-8130, Japan
Present address: Fundacion Inbiomed. Paseo Mikeletegi 61, bajo, 20009 San Sebastian, Gipuzkoa, Spain
^¶ Author for correspondence (e-mail: toda{at}icrf.icnet.uk )

Accepted May 1, 2001

Accurate chromosome segregation is dependent upon the integrity of mitotic spindles, which pull each pair of sister chromatids towards opposite poles. In this study, we have characterised fission yeast pop3-5235, a diploidising mutant that is impaired in genome stability. Pop3 is the same as Wat1, a conserved protein containing 7 WD repeats. Pop3/Wat1 has also been isolated from a two-hybrid screen as a binding partner to Prp2, the large subunit of the essential splicing factor U2AF. In wat1 mutants, the cellular amount of -tubulin is decreased to very low levels, which results in compromised microtubules and spindles, consequently leading to unequal chromosome separation. Further analysis shows that, in spite of the binding between Wat1 and Prp2, Wat1 may not be involved directly in splicing reactions per se. Instead, we find that Wat1 is required for the maintenance of -tubulin mRNA levels; moreover, transcript levels of genes other than the -tubulin gene are also equally decreased in this mutant. Wild-type Wat1, but not the mutant protein, forms a large complex in the cell with several other proteins, suggesting that Wat1 functions as a structural linker in the complex. The results suggest that Wat1 plays a role in mRNA maturation as a coupling protein between splicing and synthesis and/or stabilisation.

Key words: Fission yeast, Genome integrity, Spindle, Splicing, Transcription, WD repeats

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