Reactome | Assembly of the pre-replicative complex

Assembly of the pre-replicative complex

Stable Identifier

R-HSA-68867

DOI

10.3180/R-HSA-68867.7

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

ReviewStatus

5/5

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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 S. cerevisiae and humans has been demonstrated by chromatin immunoprecipitation experiments. In S. cerevisiae, 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, Xenopus, S. pombe, and S. cerevisiae cells.

Literature References

PubMed ID	Title	Journal	Year
9288745	Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs. Nasmyth, K, Tanaka, T, Knapp, D	Cell	1997
9829972	The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p. Zou-Yang, XH, Stillman, B, Gavin, K, Kobayashi, R, Hunt, T, Pappin, D, Canas, B, Tugal, T	J Biol Chem	1999
11801723	Mammalian nuclei become licensed for DNA replication during late telophase. Prokhorova, TA, Todorov, IT, Gilbert, DM, Blow, JJ, Dimitrova, DS	J Cell Sci	2002
9407030	Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants. Stillman, B, Liang, C	Genes Dev	1998
9927482	AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Koonin, EV, Aravind, L, Spouge, JL, Neuwald, AF	Genome Res	1999
9335335	Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Bell, SP, Aparicio, OM, Weinstein, DM	Cell	1997
11046155	Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mendez, J, Stillman, B	Mol Cell Biol	2000