Cyclin A2 is a key regulator of the cell cycle, implicated both in DNA replication and mitotic entry. Cyclin A2 participates in feedback loops that activate mitotic kinases in G2 phase, but why active Cyclin A2-CDK2 during the S phase does not trigger mitotic kinase activation remains unclear. Here, we describe a change in localisation of Cyclin A2 from being only nuclear to both nuclear and cytoplasmic at the S/G2 border. We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1. Expression of predominately cytoplasmic Cyclin A2 or phospho-mimicking PLK1 T210D can partially rescue a G2 arrest caused by Cyclin A2 depletion. Cytoplasmic presence of Cyclin A2 is restricted by p21, in particular after DNA damage. Cyclin A2 chromatin association during DNA replication and additional mechanisms contribute to Cyclin A2 localisation change in the G2 phase. We find no evidence that such mechanisms involve G2 feedback loops and suggest that cytoplasmic appearance of Cyclin A2 at the S/G2 transition functions as a trigger for mitotic kinase activation.

• MeSH
• aktivace enzymů genetika   MeSH
• buněčné jádro metabolismus   MeSH
• chromatin metabolismus   MeSH
• cyklin A2 genetika   metabolismus   MeSH
• cyklin-dependentní kinasa 2 nedostatek   genetika   MeSH
• cytoplazma metabolismus   MeSH
• fosforylace genetika   MeSH
• G2 fáze genetika   MeSH
• HeLa buňky MeSH
• lidé MeSH
• mitóza genetika   MeSH
• polo-like kinasa 1 MeSH
• poškození DNA genetika   MeSH
• protein-serin-threoninkinasy metabolismus   MeSH
• proteinkinasa CDC2 nedostatek   genetika   MeSH
• proteiny buněčného cyklu metabolismus   MeSH
• protoonkogenní proteiny metabolismus   MeSH
• S fáze genetika   MeSH
• signální transdukce genetika   MeSH
• transfekce MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bora protein, human MeSH Prohlížeč
• CCNA2 protein, human MeSH Prohlížeč
• CDK1 protein, human MeSH Prohlížeč
• CDK2 protein, human MeSH Prohlížeč
• chromatin MeSH
• cyklin A2 MeSH
• cyklin-dependentní kinasa 2 MeSH
• protein-serin-threoninkinasy MeSH
• proteinkinasa CDC2 MeSH
• proteiny buněčného cyklu MeSH
• protoonkogenní proteiny MeSH

Double-stranded DNA breaks activate a DNA damage checkpoint in G2 phase to trigger a cell cycle arrest, which can be reversed to allow for recovery. However, damaged G2 cells can also permanently exit the cell cycle, going into senescence or apoptosis, raising the question how an individual cell decides whether to recover or withdraw from the cell cycle. Here we find that the decision to withdraw from the cell cycle in G2 is critically dependent on the progression of DNA repair. We show that delayed processing of double strand breaks through HR-mediated repair results in high levels of resected DNA and enhanced ATR-dependent signalling, allowing p21 to rise to levels at which it drives cell cycle exit. These data imply that cells have the capacity to discriminate breaks that can be repaired from breaks that are difficult to repair at a time when repair is still ongoing.

• MeSH
• ATM protein genetika   metabolismus   MeSH
• buněčné linie MeSH
• časosběrné zobrazování metody   MeSH
• cyklin B1 genetika   metabolismus   MeSH
• fluorescenční mikroskopie MeSH
• HEK293 buňky MeSH
• inhibitor p21 cyklin-dependentní kinasy genetika   metabolismus   MeSH
• kontrolní body fáze G2 buněčného cyklu genetika   MeSH
• lidé MeSH
• oprava DNA genetika   MeSH
• poškození DNA * MeSH
• signální transdukce genetika   MeSH
• stárnutí buněk genetika   MeSH
• zelené fluorescenční proteiny genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ATM protein MeSH
• ATR protein, human MeSH Prohlížeč
• CCNB1 protein, human MeSH Prohlížeč
• cyklin B1 MeSH
• inhibitor p21 cyklin-dependentní kinasy MeSH
• zelené fluorescenční proteiny MeSH