Abstract
SummaryThe functions of the Ndc80/Hec1 subunit of the highly conserved Ndc80 kinetochore complex are normally restricted to M phase when it exerts a pivotal kinetochore-based role. Here, we find that in mouse oocytes, depletion of Hec1 severely compromises the G2-M transition because of impaired activation of cyclin-dependent kinase 1 (Cdk1). Unexpectedly, impaired M phase entry is due to instability of the Cdk1-activating subunit, cyclin B2, which cannot be covered by cyclin B1. Hec1 protects cyclin B2 from destruction by the Cdh1-activated anaphase-promoting complex (APCCdh1) and remains important for cyclin B2 stabilization during early M phase, required for the initial stages of acentrosomal spindle assembly. By late M phase, however, Hec1 and cyclin B2 become uncoupled, and although Hec1 remains stable, APCCdc20 triggers cyclin B2 destruction. These data identify another dimension to Hec1 function centered on M phase entry and early prometaphase progression and challenge the view that cyclin B2 is completely dispensable in mammals.
Highlights
The Ndc80 complex, comprised of the Hec1, Nuf2, Spc24, and Spc25 subunits, is a highly conserved kinetochore component (Ciferri et al, 2007)
A prominent feature of mammalian oocytes not shared with mitosis is Cdh1-activated APC activity (APCCdh1) during prophase and early prometaphase (Homer et al, 2009; Homer, 2011; Reis et al, 2006, 2007), which, by severely restraining cyclin accumulation, could limit the capacity of cyclins to cover for one another
Mammalian oocytes experience a protracted G2-prophase arrest characterized by the presence of an intact germinal vesicle (GV; Figure 1A), the term used for the oocyte’s large and identifiable nucleus
Summary
The functions of the Ndc80/Hec subunit of the highly conserved Ndc kinetochore complex are normally restricted to M phase when it exerts a pivotal kinetochore-based role. Impaired M phase entry is due to instability of the Cdk1-activating subunit, cyclin B2, which cannot be covered by cyclin B1. By late M phase, Hec and cyclin B2 become uncoupled, and Hec remains stable, APCCdc triggers cyclin B2 destruction. These data identify another dimension to Hec function centered on M phase entry and early prometaphase progression and challenge the view that cyclin B2 is completely dispensable in mammals
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