ORC or Origin Recognition Complex is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes in an ATP-dependent manner to origins of replication.

During the G1 phase of the cell cycle, when S-phase CDK

Cyclin-dependent kinase

thumb|350px|Schematic of the cell cycle. outer ring: I=[[Interphase]], M=[[Mitosis]]; inner ring: M=Mitosis; G1=[[G1 phase|Gap phase 1]]; S=[[S phase|Synthesis]]; G2=[[G2 phase|Gap phase 2]]...

 levels are low, ORC recruits Cdc6

Cdc6

Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...

 and Cdt1.

One Cdc6

Cdc6

Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...

 and one Cdt1 bind to each strand of DNA. Cdc6

Cdc6

Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...

 and Cdt1 interact with each other and inhibit Mcm

Mini Chromosome Maintenance

Mini Chromosome Maintenance complex, or Minichromosome Maintenance protein complex or mini-chromosome maintenance 2-7 helicase complex has a role in both the initiation and the elongation phases of eukaryotic DNA replication, specifically the formation and elongation of the replication fork...

, a DNA helicase that binds after Cdc6

Cdc6

Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...

 and Cdt1 binding to the ORC.

The ORC, Cdc6

Cdc6

Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...

, Cdt1 and Mcm

Mini Chromosome Maintenance

Mini Chromosome Maintenance complex, or Minichromosome Maintenance protein complex or mini-chromosome maintenance 2-7 helicase complex has a role in both the initiation and the elongation phases of eukaryotic DNA replication, specifically the formation and elongation of the replication fork...

 proteins form the Pre-replication complex

Pre-replication complex

A pre-replication complex is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the...

.

Activated S-CDK triggers S-phase and phosphorylates Cdc6

Cdc6

Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...

.

Phosphorylated Cdc6

Cdc6

Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...

 is degraded.

Cdt1 is inhibited by geminin

Geminin

Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the GMNN gene.Geminin is a nuclear protein that is present in most eukaryotics and highly conserved across species...

.

With Cdc6

Cdc6

Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...

 and Cdt1 no longer bound, Mcm

Mini Chromosome Maintenance

Mini Chromosome Maintenance complex, or Minichromosome Maintenance protein complex or mini-chromosome maintenance 2-7 helicase complex has a role in both the initiation and the elongation phases of eukaryotic DNA replication, specifically the formation and elongation of the replication fork...

 can unwind the double stranded DNA allowing the preinitiation complex

Preinitiation complex

The preinitiation complex is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes...

 to bind.

ORC is phosphorylated and DNA replication

DNA replication

DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

 takes place.

DDK also participates in ORC activation and triggers the transition into DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

replication.