[5][6][7] ORC and Noc3p bound at replication origins serve as the foundation for assembly of the pre-replication complex (pre-RC), which includes Cdc6, Tah11 (a.k.a.
[8][9][10][11] Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase.
[12][13][14] Cell cycle-regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase.
[4][15][16][17] The ORC is present throughout the cell cycle bound to replication origins, but is only active in late mitosis and early G1.
[4] A 2020 report suggests that budding yeast ORC dimerizes in a cell cycle dependent manner to control licensing.
[28] Autonomously Replicating Sequences (ARS), first discovered in budding yeast, are integral to the success of the ORC.
A highly conserved sequence of 11bp (known as the A element) is thought to be essential for origin function in budding yeast.
These replicons all have similar basic residues to which the ORC binds, which in many ways mimic the conserved 11bp A element.
First, the ORC, Noc3p and Cdc6 form a complex on origin DNA (marked by ARS type regions).
In S phase, the Mcm2-7 complex interacts with helicase cofactors Cdc45 and GINS to isolate a single DNA strand, unwind the origin, and begin replication down the chromosome.