InterPro domain: IPR016314

This group represents the cell division control protein Cdc6 and Cdc18, which are essential initiation factors for DNA replication [ 1 ].

Cdc6 appears to have an important and perhaps unique dual role in S phase, it is first required for the initiation of DNA replication and then actively participates in the suppression of nuclear division. It interacts with the origin recognition complex (ORC). It targeted for degradation by the E3 ubiquitin ligase complex SCF (Cdc4) [ 2 , 3 ].

Cdc18 is part of the checkpoint control that prevents mitosis from occurring until S phase is completed. It plays a key role in coupling S phase to start and mitosis. It acts at the initiation of DNA replication and plays a major role in controlling the onset of S-phase. Together with orp1, it is involved in the maintenance of replication forks and activation of cds1-dependent S-phase checkpoint [ 4 , 5 , 6 , 7 , 8 ].

1. Expression of Cdc18/Cdc6 and Cdt1 during G2 phase induces initiation of DNA replication. EMBO J. 20, 4648-56
2. Dual functions of CDC6: a yeast protein required for DNA replication also inhibits nuclear division. EMBO J. 11, 2167-76
3. The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. EMBO J. 16, 5966-76
4. The fission yeast cdc18+ gene product couples S phase to START and mitosis. Cell 74, 371-82
5. p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast. Cell 83, 397-405
6. Fission yeast WD-repeat protein pop1 regulates genome ploidy through ubiquitin-proteasome-mediated degradation of the CDK inhibitor Rum1 and the S-phase initiator Cdc18. Genes Dev. 11, 1548-60
7. The Cdt1 protein is required to license DNA for replication in fission yeast. Nature 404, 625-8
8. Maintenance of replication forks and the S-phase checkpoint by Cdc18p and Orp1p. Nat. Cell Biol. 4, 384-8