Cdc20 (cell division cycle 20) and Cdh1 are the activating subunits of APC (anaphase-promoting complex), an E3-ubiquitin ligase that drives cells into anaphase by inducing degradation of cyclin B and the anaphase inhibitor securin. To prevent chromosome missegregation due to early degradation of cyclin B and securin, mitotic checkpoint protein complexes consisting of BubR1, Bub3 and Mad2 bind to and inhibit APCCdc20 until all chromosomes are properly attached to the mitotic spindle and aligned in the metaphase plate. The nuclear transport factors Rae1 and Nup98, which convert into mitotic checkpoint proteins in M-phase, further prevent chromosome missegregation by assembling into a complex with APCCdh1 and delaying APCCdh1-mediated ubiquitination of securin. Disruption of Mad2, BubR1, Bub3 or Rae1 in mice results in substantial aneuploidy in somatic tissues, but whether these genes are equally important for accurate chromosome segregation during meiosis has not yet been established. To address this issue, we generated cohorts of male mice in which Mad2, BubR1, Bub3, Rae1 and Nup98 were disrupted either individually or in combination. We tested the fertility of these mice and performed chromosome counts on secondary spermatocytes. We found that male fertility and accurate chromosome segregation during spermatogenesis are highly dependent on BubR1, but not Mad2, Bub3, Rae1 and Nup98. Our results suggest that the mechanisms ensuring accurate chromosome segregation differ between mitotic and meiotic cells.
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Conference Article|
July 21 2006
Differential mitotic checkpoint protein requirements in somatic and germ cells
K.B. Jeganathan;
K.B. Jeganathan
1Department of Pediatric and Adolescent Medicine, Mayo College of Medicine, 200 First Street SW, Rochester, MN 55905, U.S.A., and Department of Biochemistry and Molecular Biology, Mayo College of Medicine, 200 First Street SW, Rochester, MN 55905, U.S.A.
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J.M. van Deursen
J.M. van Deursen
1
1Department of Pediatric and Adolescent Medicine, Mayo College of Medicine, 200 First Street SW, Rochester, MN 55905, U.S.A., and Department of Biochemistry and Molecular Biology, Mayo College of Medicine, 200 First Street SW, Rochester, MN 55905, U.S.A.
1To whom correspondence should be addressed (email vandeursen.jan@mayo.edu).
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Publisher: Portland Press Ltd
Received:
March 13 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (4): 583–586.
Article history
Received:
March 13 2006
Citation
K.B. Jeganathan, J.M. van Deursen; Differential mitotic checkpoint protein requirements in somatic and germ cells. Biochem Soc Trans 1 August 2006; 34 (4): 583–586. doi: https://doi.org/10.1042/BST0340583
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