Mutations in the Essential Spindle Checkpoint Gene bub1 Cause Chromosome Missegregation and Fail to Block Apoptosis in Drosophila

doi:10.1083/jcb.146.1.13

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J. Cell Biol., Volume 146, Number 1, July 12, 1999 13-28
Copyright © 1999 by The Rockefeller University Press.

Mutations in the Essential Spindle Checkpoint Gene bub1 Cause Chromosome Missegregation and Fail to Block Apoptosis in Drosophila

Joydeep Basu^a, Hassan Bousbaa^b, Elsa Logarinho^b, ZeXiao Li^a, Byron C. Williams^a, Carla Lopes^b, Claudio E. Sunkel^b,c, and Michael L. Goldberg^a
^a Section of Genetics and Development, Cornell University, Ithaca, New York 14853
^b Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150 Porto, Portugal
^c Instituto de Abel Salazar, Universidade do Porto, 4050 Porto, Portugal

Correspondence to: Michael L. Goldberg, Section of Genetics and Development, Biotechnology Building, Cornell University, Ithaca, NY 14853., mlg11{at}cornell.edu (E-mail), (607) 254-4802 (phone), (607) 255-6249 (fax)

We have characterized the Drosophila mitotic checkpoint controlprotein Bub1 and obtained mutations in the bub1 gene. DrosophilaBub1 localizes strongly to the centromere/kinetochore of mitoticand meiotic chromosomes that have not yet reached the metaphaseplate. Animals homozygous for P-element–induced, near-nullmutations of bub1 die during late larval/pupal stages due tosevere mitotic abnormalities indicative of a bypass of checkpointfunction. These abnormalities include accelerated exit frommetaphase and chromosome missegregation and fragmentation. Chromosomefragmentation possibly leads to the significantly elevated levelsof apoptosis seen in mutants.

We have also investigated the relationship between Bub1 andother kinetochore components. We show that Bub1 kinase activityis not required for phosphorylation of 3F3/2 epitopes at prophase/prometaphase,but is needed for 3F3/2 dephosphorylation at metaphase. Neither3F3/2 dephosphorylation nor loss of Bub1 from the kinetochoreis a prerequisite for anaphase entry. Bub1's localization tothe kinetochore does not depend on the products of the geneszw10, rod, polo, or fizzy, indicating that the kinetochore isconstructed from several independent subassemblies.

Key Words: checkpoint, kinetochore, chromosome missegregation, apoptosis

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