1 Administration, BRIC Administration, BRIC, Københavns Universitet2 Helin Group, BRIC Research Groups, BRIC, Københavns Universitet3 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.4 unknown5 BRIC Administration, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet6 BRIC Administration, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet
Cdc10-dependent transcript 1 (Cdt1) is an essential DNA replication protein whose accumulation at the end of the cell cycle promotes the formation of pre-replicative complexes and replication in the next cell cycle. Geminin is thought to be involved in licensing replication by promoting the accumulation of Cdt1 in mitosis, because decreasing the Geminin levels prevents Cdt1 accumulation and impairs DNA replication. Geminin is known to inhibit Cdt1 function; its depletion during G2 leads to DNA rereplication and checkpoint activation. Here we show that, despite rapid Cdt1 protein turnover in G2 phase, Geminin promotes Cdt1 accumulation by increasing its RNA and protein levels in the unperturbed cell cycle. Therefore, Geminin is a master regulator of cell-cycle progression that ensures the timely onset of DNA replication and prevents its rereplication.