Yeast Genetics and Molecular Biology 1998
College Park, Maryland
August 1998


Name: Balasundaram, David
Mailing Address: LEGR, NICHD, NIH, Bldg 6B, R 220, Bethesda, MD 20892, USA
Email Address: davidb@box-d.nih.gov
Phone and Fax numbers: (301)402-4282, (301) 496-8576

026

A mutation in a nuclear pore factor of fission yeast specifically inhibits nuclear import of the retrotransposon Tf1.


David Balasundaram (1) , Michael Benedik (2), Henry Levin (3)
(1) Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892; (2) University of Houston, Houston TX 77204-5934.; (3) LEGR, NICHD, NIH, Bldg 6B, R 220, Bethesda, MD 20892, USA

Because the nuclear envelope of Schizosaccharomyces pombe remains intact throughout the cell cycle, the cDNA and integrase complexes of the LTR-retrotransposon Tf1 must be transported through an intact nuclear envelope to enter the nucleus. S. Pombe genes with mutations that could potentially cause defects in the nuclear import of Tf1 cDNA were identified with a recombination assay. One strain with a 12-fold defect in transposition exhibited a 42-fold reduction in homologous recombination of Tf1 cDNA. Genetic analysis of this strain revealed that the defects in transposition and recombination were due to a mutation in an essential gene that we have named nup124. nup124 is related to a family of nucleopore proteins that possess multiple copies of FXFG motifs that bind nuclear import receptors to the nuclear pore. The prediction that nup124 is indeed a component of the nuclear pore was supported by immunofluorescence microscopy. We also used immunofluorescence microscopy to ask whether the mutation in nup124 inhibited nuclear import of any Tf1 complexes. Tf1 Gag produced a prominent signal from 74% of the wild-type nuclei. An equivalent signal was seen in only 8% of the mutant nuclei. Because mutant cells grew with wild-type rates, and because the localization of known nuclear proteins was normal in the mutant strains, the mutation in nup124 appears to specifically inhibit Tf1 import without significantly reducing bulk nuclear import of cellular proteins. Purified Gag fused to GST interacted directly with the N-terminal half of nup124. This interaction suggests a direct and specific role for nup124 in the nuclear import of Tf1.


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