Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis

Aurora-A は細胞分裂期においてgeminin を安定化することで複製前複合体形成やDNA複製を制御する

Tsunematsu Takaaki

Geminin, an essential factor for DNA replication, directly binds to the licensing factor Cdt1 and inhibits pre-replicative complex (pre-RC) formation to prevent re-replication. In G1, geminin levels are controlled by the anaphase-promoting complex/cyclosome ubiquitin ligase complex (APC/C), which targets geminin for proteasomal degradation to allow pre-RC formation. Conversely, from S to G2, geminin is stabilized thanks to APC/C inhibition to ensure inhibition of pre-RC 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-mediated degradation during mitosis. In turn, stabilized geminin inhibits SCFSkp2-mediated degradation of Cdt1 to ensure pre-RC formation in the ensuing S phase. The Aurora-A-geminin-Cdt1 axis therefore represents a critical regulator of proper DNA replication.

Medical sciences [ 490 ]

eng

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[Created] 2014-11-21

Takaaki Tsunematsu, Yoshihiro Takihara, Naozumi Ishimaru, Michele Pagano, Takashi Takata & Yasusei Kudo; Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis; Nature Communications Volume 4, Article number 1885 (doi: 10.1038/ncomms2859) references

[DOI] http://dx.doi.org/10.1038/ncomms2859 references

広島大学