Appropriate expression of Ube2C and Ube2S controls the progression of the first meiotic division.

Timely degradation of protein regulators of the cell cycle is essential for the completion of cell division. This degradation is promoted by the E3 anaphase-promoting complex/cyclosome (APC/C) and mediated by the E2 ubiquitin-conjugating enzymes (Ube2s). Unlike the ample information gathered regarding the meiotic E3 APC/C, the E2s participating in this cell division have never been studied. We identified Ube2C, -S, and -D3 as the E2 enzymes that regulate APC/C activity during meiosis of mouse oocytes. Their depletion reduces the levels of the first meiotic cytokinesis by 50%, and their overexpression doubles and accelerates its completion (50% as compared with 4% at 11 h). We also demonstrated that these E2s take part in ensuring appropriate spindle formation. It is noteworthy that high levels of Ube2C bring about the resumption of the first meiotic division, regardless of the formation of the spindle, overriding the spindle assembly checkpoint. Thus, alongside their canonical function in protein degradation, Ube2C and -S also control the extrusion of the first polar body. Overall, our study characterizes new regulators and unveils the novel roles they play during the meiotic division. These findings shed light on faithful chromosome segregation in oocytes and may contribute to better understanding of aneuploidy and its consequent genetic malformations.