Bub 3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis

Bub3 is a conserved component of the mitotic spindle assembly complex. The protein is essential for early development in Bub3 gene-disrupted mice, evident from their failure to survive beyond day 6.5–7.5 postcoitus (pc). Bub3 null embryos appear normal up to day 3.5 pc but accumulate mitotic errors from days 4.5–6.5 pc in the form of micronuclei, chromatin bridging, lagging chromosomes, and irregular nuclear morphology. Null embryos treated with a spindle-depolymerising agent fail to arrest in metaphase and show an increase in mitotic disarray. The results confirm Bub3 as a component of the essential spindle checkpoint pathway that operates during early embryogenesis.

[1]  P. Sorger,et al.  Chromosome Missegregation and Apoptosis in Mice Lacking the Mitotic Checkpoint Protein Mad2 , 2000, Cell.

[2]  D. Brady,et al.  Complex formation between Mad1p, Bub1p and Bub3p is crucial for spindle checkpoint function , 2000, Current Biology.

[3]  K. Choo,et al.  Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  G. Chan,et al.  Human Bubr1 Is a Mitotic Checkpoint Kinase That Monitors Cenp-E Functions at Kinetochores and Binds the Cyclosome/APC , 1999, The Journal of cell biology.

[5]  P. Sorger,et al.  Retention of the BUB3 checkpoint protein on lagging chromosomes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  C. Sunkel,et al.  Mutations in the Essential Spindle Checkpoint Gene bub1 Cause Chromosome Missegregation and Fail to Block Apoptosis in Drosophila , 1999, The Journal of cell biology.

[7]  K. Choo,et al.  Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice. , 1999, Human molecular genetics.

[8]  A. Amon The spindle checkpoint. , 1999, Current opinion in genetics & development.

[9]  C. Sunkel,et al.  Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod , 1998, Chromosoma.

[10]  Andrew W. Murray,et al.  Spindle Checkpoint Protein Xmad1 Recruits Xmad2 to Unattached Kinetochores , 1998, The Journal of cell biology.

[11]  Stephen S. Taylor,et al.  The Human Homologue of Bub3 Is Required for Kinetochore Localization of Bub1 and a Mad3/Bub1-related Protein Kinase , 1998, The Journal of cell biology.

[12]  A. Murray,et al.  Microinjection of Antibody to Mad2 Protein into Mammalian Cells in Mitosis Induces Premature Anaphase , 1998, The Journal of cell biology.

[13]  A. Murray,et al.  Localization of Mad2 to Kinetochores Depends on Microtubule Attachment, Not Tension , 1998, The Journal of cell biology.

[14]  M. Hoyt,et al.  Bub1p Kinase Activates the Saccharomyces cerevisiae Spindle Assembly Checkpoint , 1998, Molecular and Cellular Biology.

[15]  N. Morris,et al.  A screen for dynein synthetic lethals in Aspergillus nidulans identifies spindle assembly checkpoint genes and other genes involved in mitosis. , 1998, Genetics.

[16]  Bert Vogelstein,et al.  Mutations of mitotic checkpoint genes in human cancers , 1998, Nature.

[17]  K. Choo,et al.  Targeted disruption of mouse centromere protein C gene leads to mitotic disarray and early embryo death. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Stephen S. Taylor,et al.  Kinetochore Localization of Murine Bub1 Is Required for Normal Mitotic Timing and Checkpoint Response to Spindle Damage , 1997, Cell.

[19]  Andrew W. Murray,et al.  Association of Spindle Assembly Checkpoint Component XMAD2 with Unattached Kinetochores , 1996, Science.

[20]  R. Benezra,et al.  Identification of a Human Mitotic Checkpoint Gene: hsMAD2 , 1996, Science.

[21]  Eric L. Weiss,et al.  The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint , 1996, The Journal of cell biology.

[22]  B. Roberts,et al.  The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. , 1994, Molecular and cellular biology.

[23]  Temple F. Smith,et al.  The ancient regulatory-protein family of WD-repeat proteins , 1994, Nature.

[24]  B. Roberts,et al.  S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function , 1991, Cell.

[25]  Andrew W. Murray,et al.  Feedback control of mitosis in budding yeast , 1991, Cell.

[26]  P. Hieter,et al.  Kinetochores and the checkpoint mechanism that monitors for defects in the chromosome segregation machinery. , 1998, Annual review of genetics.

[27]  K. Choo,et al.  A functional neo-centromere formed through activation of a latent human centromere and consisting of non-alpha-satellite DNA , 1997, Nature Genetics.