Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 583-586 |
| Number of pages | 4 |
| Journal | Biochemical Society Transactions |
| Volume | 34 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 2006 |
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Keywords
- Age-related infertility
- Anaphase-promoting complex
- Aneuploidy
- Chromosome missegregation
- Somatic cell
- Spindle assembly checkpoint
ASJC Scopus subject areas
- Biochemistry
Cite this
Differential mitotic checkpoint protein requirements in somatic and germ cells. / Jeganathan, K. B.; Van Deursen, Jan.
In: Biochemical Society Transactions, Vol. 34, No. 4, 08.2006, p. 583-586.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential mitotic checkpoint protein requirements in somatic and germ cells
AU - Jeganathan, K. B.
AU - Van Deursen, Jan
PY - 2006/8
Y1 - 2006/8
N2 - 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.
AB - 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.
KW - Age-related infertility
KW - Anaphase-promoting complex
KW - Aneuploidy
KW - Chromosome missegregation
KW - Somatic cell
KW - Spindle assembly checkpoint
UR - http://www.scopus.com/inward/record.url?scp=33747177050&partnerID=8YFLogxK
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U2 - 10.1042/BST0340583
DO - 10.1042/BST0340583
M3 - Article
VL - 34
SP - 583
EP - 586
JO - Biochemical Society Transactions
JF - Biochemical Society Transactions
SN - 0300-5127
IS - 4
ER -