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- Title
Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis.
- Authors
Tsunematsu, Takaaki; Takihara, Yoshihiro; Ishimaru, Naozumi; Pagano, Michele; Takata, Takashi; Kudo, Yasusei
- Abstract
Geminin, an essential factor for DNA replication, directly binds to the licensing factor Cdt1 and inhibits pre-replicative complex formation to prevent re-replication. In G1, geminin levels are controlled by the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex, which targets geminin for proteasomal degradation to allow pre-replicative complex formation. Conversely, from S to G2, geminin is stabilized due to APC/C ubiquitin ligase complex inhibition, ensuring the inhibition of pre-replicative complex formation. However, mitotic regulation of geminin has hitherto not been described. Here we show that Aurora-A phosphorylates geminin on Thr25 during M phase, and this event induces geminin stabilization by preventing its APC/C ubiquitin ligase complex-mediated degradation during mitosis. In turn, stabilized geminin inhibits SCFSkp2-mediated degradation of Cdt1 to ensure pre-replicative complex formation in the ensuing S phase. The Aurora-A-geminin-Cdt1 axis therefore represents a critical regulator of proper DNA replication.
- Publication
Nature Communications, 2013, Vol 4, Issue 5, p1885
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/ncomms2859