PathwayStep448 PathwayStep449 PathwayStep456 PathwayStep457 PathwayStep452 Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC) Association of MCM8 with ORC:origin complex CDT1 association with the CDC6:ORC:origin complex Assembly of the pre-replicative complex Authored: Davey, MJ, O'Donnell, M, Tye, BK, 2006-03-17 16:01:39 DNA replication pre-initiation in eukaryotic cells begins with the formation of the pre-replicative complex (pre-RC) during the late M phase and continues in the G1 phase of the mitotic cell cycle, a process also called DNA replication origin licensing. The association of initiation proteins (ORC, Cdc6, Cdt1, Mcm2-7) with the origin of replication in both <i>S. cerevisiae</i> and humans has been demonstrated by chromatin immunoprecipitation experiments. In <i>S. cerevisiae</i>, pre-replicative complexes are assembled from late M to G1. In mammalian cells as well, pre-replicative complexes are assembled from late M to G1, as shown by biochemical fractionation and immunostaining. There are significant sequence similarities among some of the proteins in the pre-replicative complex. The ORC subunits Orc1, Orc4 and Orc5 are homologous to one another and to Cdc6. The six subunits of the Mcm2-7 complex are homologous to one another. In addition, Orc1, Orc4, Orc5, Cdc6, and the Mcm2-7 subunits, are members of the AAA+ superfamily of ATPases. Since the initial identification of these pre-RC components other factors that participate in this complex have been found, including Cdt1 in human, <i>Xenopus</i>, <i>S. pombe</i>, and <i>S. cerevisiae</i> cells. Pubmed11046155 Pubmed11801723 Pubmed9288745 Pubmed9335335 Pubmed9407030 Pubmed9829972 Pubmed9927482 Reactome Database ID Release 4368867 Reactome, http://www.reactome.org ReactomeREACT_2243 CDC6 association with the ORC:origin complex Assembly of the ORC complex at the origin of replication