 After promoting initiation of eukaryotic DNA replication at the origin, Cdt1 is inactivated by Geminin and targeted for degradation by the SCFSkp2 and CRL4Cdt2 complexes.Cdt1 expression is stabilized by RNAi-mediated knockdown of DDB1 or both CUL4A and CUL4B, which suggests redundant or overlapping function of the two CUL4 proteins for Cdt1 regulation.Only reduction of Geminin expression seems to induce re-replication in Cdt1-overexpressing cells.