CENP-F-dependent DRP1 function regulates APC/C activity during oocyte meiosis I

Abstract

Chromosome segregation is initiated by cohesin degradation, which is driven by anaphase-promoting complex/cyclosome (APC/C). Chromosome cohesin is removed by activated separase, with the degradation of securin and cyclinB1. Dynamin-related protein 1 (DRP1), a component of the mitochondrial fission machinery, is related to cyclin dynamics in mitosis progression. Here, we show that DRP1 is recruited to the kinetochore by centromeric Centromere protein F (CENP-F) after nuclear envelope breakdown in mouse oocytes. Loss of DRP1 during prometaphase leads to premature cohesin degradation and chromosome segregation. Importantly, acute DRP1 depletion activates separase by initiating cyclinB1 and securin degradation during the metaphase-to-anaphase transition. Finally, we demonstrate that DRP1 is bound to APC2 to restrain the E3 ligase activity of APC/C. In conclusion, DRP1 is a CENP-F-dependent atypical spindle assembly checkpoint (SAC) protein that modulates metaphase-to-anaphase transition by controlling APC/C activity during meiosis I in oocytes.

KAT8 functions in redox homeostasis and mitochondrial dynamics during mouse oocyte meiosis progression

“…Under the luteinizing hormone (LH) surge, immature oocytes resume meiosis and undergo germinal vesicle breakdown (GVBD), followed by pairing chromosomes on the equatorial plate and microtubule organization. Subsequently, the first polar body (Pb1) is extruded, and the eggs are arrested at metaphase II (MII) until fertilization 2–4 . Any error in this process causes embryonic developmental arrest and implantation failure, resulting in spontaneous abortion of the fetus or the birth of chromosomally unbalanced offspring 5 .…”

“…Subsequently, the first polar body (Pb1) is extruded, and the eggs are arrested at metaphase II (MII) until fertilization. [2][3][4] Any error in this process causes embryonic developmental arrest and…”