LIG1
UniProt:P18858 LIG1
FEN1
RAD2
UniProt:P39748 FEN1
MCM8
UniProt:Q9UJA3 MCM8
CDC6 association with ORC:origin complexes mediated by MCM8
The geminin component of geminin:Cdt1 complexes is ubiquitinated, releasing Cdt1
Ubiquitinated geminin is degraded by the proteasome
Free CDT1 associates with CDC6:ORC:origin complexes
Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC)
Mcm10 associates with the pre-replicative complex, stabilizing Mcm2-7
Cdt1 is displaced from the pre-replicative complex.
CDK and DDK associate with the Mcm10:pre-replicative complex
Mcm2-7 is phosphorylated by DDK
Cdc45 associates with the pre-replicative complex at the origin
DNA Replication Factor A (RPA) associates with the pre-replicative complex at the origin
DNA polymerase alpha:primase binds at the origin
DNA polymerase epsilon binds at the origin
The primase component of DNA polymerase:primase synthesizes a 6-10 nucleotide RNA primer at the origin
The polymerase component of DNA polymerase alpha:primase synthesizes a 20-nucleotide primer at the origin
Orc1 is phosphorylated by cyclin A/CDK2
Phosphorylated Orc1 is ubiquitinated while still associated with chromatin
Ubiquitinated Orc1 enters the cytosol
Ubiquitinated Orc1 is degraded by the proteasome
Cdc6 protein is phosphorylated by CDK
Phosphorylated Cdc6 is exported from the nucleus
Cytoplasmic phosphorylated Cdc6 is ubiquitinated by the anaphase-promoting complex
Ubiquitinated Cdc6 is degraded by the proteasome
Mcm4,6,7 trimer forms and associates with the replication fork
Rearrangement and mobilization of Mcm2-7
MCM2-7 mediated fork unwinding
MCM8 mediated fork unwinding
Formation of GINS complex
Multiple proteins are localized at replication fork
RFC binding displaces Pol Alpha
Loading of PCNA - Sliding Clamp Formation
Orc3 associates with Orc2 constitutively bound at origins of replication
RFC dissociates after sliding clamp formation
Formation of Processive Complex
Processive synthesis on the leading strand
Formation of Okazaki fragments
Formation of the Flap Intermediate
RPA binds to the Flap
Recruitment of Dna2 endonuclease
Removal of RNA primer and dissociation of RPA and Dna2
Removal of remaining Flap
Joining of adjacent Okazaki fragments
Orc5 associates with Orc3:Orc2:origin complexes
Cdt1 associates with geminin
Orc4 associates with Orc5:Orc3:Orc2:origin complexes
Orc1 associates with Orc4:Orc5:Orc3:Orc2:origin complexes
Orc6 associates with Orc1:Orc4:Orc5:Orc3:Orc2:origin complexes, forming ORC:origin complexes
Association of MCM8 with ORC:origin complex
DNA Replication
DNA replication initiation
Switching of origins to a post-replicative state
Orc1 removal from chromatin
CDK-mediated phosphorylation and removal of Cdc6
DNA strand elongation
Unwinding of DNA
Leading Strand Synthesis
Polymerase switching
Lagging Strand Synthesis
Processive synthesis on the lagging strand
M/G1 Transition
Removal of the Flap Intermediate
Regulation of DNA replication
Association of licensing factors with the pre-replicative complex
Removal of licensing factors from origins
DNA Replication Pre-Initiation
Assembly of the pre-replicative complex
Assembly of the ORC complex at the origin of replication
CDC6 association with the ORC:origin complex
CDT1 association with the CDC6:ORC:origin complex
Activation of the pre-replicative complex
Synthesis of DNA
CDC6 protein is synthesized under the control of E2F transcription factors