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Vol. 8, Issue 12, 2677-2691, December 1997
Department of Genetics, Stanford University School of Medicine,
Stanford, California 94305
A previously uncharacterized yeast gene (YER016w)
that we have named BIM1 (binding to microtubules) was
obtained from a two-hybrid screen of a yeast cDNA library using as bait
the entire coding sequence of TUB1 (encoding
-tubulin). Deletion of BIM1 results in a strong
bilateral karyogamy defect, hypersensitivity to benomyl, and aberrant
spindle behavior, all phenotypes associated with mutations affecting
microtubules in yeast, and inviability at extreme temperatures (i.e.,
37°C or 
14°C). Overexpression of BIM1 in
wild-type cells is lethal. A fusion of Bim1p with green fluorescent
protein that complements the bim1
phenotypes allows visualization in vivo of both intranuclear spindles and extranuclear microtubules in otherwise wild-type cells. A bim1
deletion displays synthetic lethality with deletion alleles of
bik1, num1, and bub3 as
well as a limited subset of tub1 conditional-lethal
alleles. A systematic study of 51 tub1 alleles suggests
a correlation between specific failure to interact with Bim1p in the
two-hybrid assay and synthetic lethality with the
bim1 allele. The sequence of BIM1
shows substantial similarity to sequences from organisms across the
evolutionary spectrum. One of the human homologues, EB1, has been
reported previously as binding APC, itself a microtubule-binding protein and the product of a gene implicated in the etiology of human
colon cancer.
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