Autor(es): Afonso, O ; Castellani, CM ; Cheeseman, LP ; Ferreira, JG ; Orr, B ; Ferreira, LT ; Chambers, JJ ; Morais-de-Sá, E ; Maresca, TJ ; Maiato, H
Data: 2019
Identificador Persistente: https://hdl.handle.net/10216/136252
Origem: Repositório Aberto da Universidade do Porto
Assunto(s): Aurora B; Cdk1; Cyclin B1; D. melanogaster; anaphase; cell biology; human; mitosis; mitotic exit; mouse
According to the prevailing ‘clock’ model, chromosome decondensation and nuclear envelope reformation when cells exit mitosis are byproducts of Cdk1 inactivation at the metaphase-anaphase transition, controlled by the spindle assembly checkpoint. However, mitotic exit was recently shown to be a function of chromosome separation during anaphase, assisted by a midzone Aurora B phosphorylation gradient-the ‘ruler’ model. Here we found that Cdk1 remains active during anaphase due to ongoing APC/CCdc20- and APC/CCdh1-mediated degradation of B-type Cyclins in Drosophila and human cells. Failure to degrade B-type Cyclins during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1-Cdk1 localized at the spindle midzone in an Aurora B-dependent manner, with incompletely separated chromosomes showing the highest Cdk1 activity. Slowing down anaphase chromosome motion delayed Cyclin B1 degradation and mitotic exit in an Aurora B-dependent manner. Thus, a crosstalk between molecular ‘rulers’ and ‘clocks’ licenses mitotic exit only after proper chromosome separation.
