Cyclin B3 activates the Anaphase-Promoting Complex/Cyclosome in meiosis and mitosis

by Damien Garrido, Mohammed Bourouh, Éric Bonneil, Pierre Thibault, Andrew Swan, Vincent Archambault

In mitosis and meiosis, chromosome segregation is triggered by the Anaphase-Promoting Complex/Cyclosome (APC/C), a multi-subunit ubiquitin ligase that targets proteins for degradation, leading to the separation of chromatids. APC/C activation requires phosphorylation of its APC3 and APC1 subunits, which allows the APC/C to bind its co-activator Cdc20. The identity of the kinase(s) responsible for APC/C activationin vivo is unclear. Cyclin B3 (CycB3) is an activator of the Cyclin-Dependent Kinase 1 (Cdk1) that is required for meiotic anaphase in flies, worms and vertebrates. It has been hypothesized that CycB3-Cdk1 may be responsible for APC/C activation in meiosis but this remains to be determined. UsingDrosophila, we found that mutations inCycB3 genetically enhance mutations intws, which encodes the B55 regulatory subunit of Protein Phosphatase 2A (PP2A) known to promote mitotic exit. Females heterozygous forCycB3 andtws loss-of-function alleles lay embryos that arrest in mitotic metaphase in a maternal effect, indicating that CycB3 promotes anaphase in mitosis in addition to meiosis. This metaphase arrest is not due to the Spindle Assembly Checkpoint (SAC) because mutation ofmad2 that inactivates the SAC does not rescue the development of embryos fromCycB3-/+,tws-/+ females. Moreover, we found that CycB3 promotes APC/C activity and anaphase in cells in culture. We show tha...

Source: PLoS Genetics - November 2, 2020 Category: Genetics & Stem Cells Authors: Damien Garrido Source Type: research