Cell division cycle 6 (Cdc6), also named YJL194W, is a protein essential for the initiation of DNA replication. Furthermore, it is also required for the assembly and maintenance of the pre-replicative complex (pre-RC) for origin licensing. Its role is to recruit a complex of six proteins, called the mini chromosome maintenance complex. In pre- RC formation, Cdc6p acts as a loading factor for the MCM 2-7 proteins ^[1]. Cdc6 interacts with both ORC and Cdt1 protein to accomplish MCM recruitment. The MCM complex has the ability to unwind the DNA helix, this action is called helicase activity. Transcriptional repression of Cdc6 prevents pre-RC formation and initiation of DNA synthesis ^[2].

In mammalian cells, Cdc6 localizes in the cell nucleus during cell cycle G1 phase, and in some experimental situations, for example emerging mechanisms of eukaryotic DNA replication iniation, translocates to the cytoplasm at the start of S phase. In normal cells it appears that Cdc6 remains nuclear throughout the cell cycle. Cdc6 mRNA and protein levels peak at M/G1 transition when pre- RCs are formed ^[3]. In yeast cells, the Cdc6 protein is broken down during S phase rather than exported. In mammalian cells, Cdc6 is broken down during cell division. It is found that many cancers overproduce Cdc6.

http://www.ncbi.nlm.nih.gov/pubmed/9914182 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=48811 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=556684

• DNA replication
• Eukaryotic DNA replication
• Cdt1
• Mini Chromosome Maintenance

References

1. ↑ (Leatherwood J (1998) Emerging mechanisms of eukaryotic DNA replication iniation).
2. ↑ (Hogan E and Koshland D (1992) Addition of extra origins of replication to a minichromosome suppresses its mitotic loss in Cdc6 and Cdc 14 of Saccharomyces cerevisiae.)
3. ↑ (Bueno A and Russell P 1992 Dual functions of Cdc6: a yeast protein required for DNA replication also inhibits nuclear division.)