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 S phase and mitosis. It is part of the pre-replicative complex (pre-RC) and is required for loading mini chromosome maintenance (MCM) proteins onto the DNA, an essential step in the initiation of DNA synthesis. In addition, it’s a member of the family of AAA+ ATPases and highly associated to Orc1p.

Function

Cdc6p is an ATP binding protein and a member of the pre-replicative complex (pre-RC) together with the origin recognition complex (ORC), Cdt1 and the MCM complex (containing MCM2-7p). Cdc6p assembles after ORC in an ATP dependent manner and is required for loading MCM proteins onto the DNA. Reconstruction of electron microscope images showed that the ORC-Cdc6p complex forms a ring-shaped structure with similar dimensions to those of ring-shaped MCM helicase. It is thought that the Cdc6p-Cdt1 complex uses ATP hydrolysis to thread DNA through the central hole of the MCM doughnut. Mutations in the binding motif of Cdc6p strongly suggest that ATP binding and hydrolysis is essential for its function. The minimal requirement for DNA binding has been mapped within its 47-amino acid sequence. Furthermore, Cdc6 indirectly inhibits activation of the p34cdc2/CDC28 M phase kinase, thus nuclear division is suppressed.

CDC6

Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene.

The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. This protein functions as a regulator at the early steps of DNA replication. It localizes in the cell nucleus during cell cycle phase G1, but translocates to the cytoplasm at the start of S phase. The subcellular translocation of this protein during the cell cycle is regulated through its phosphorylation by cyclin-dependent kinases. Transcription of this protein was reported to be regulated in response to mitogenic signals through a transcriptional control mechanism involving E2F proteins.

Interactions

CDC6 has been shown to interact with ORC1L,ORC2L,Cyclin A2,PPP2R3B,MCM3,PPP2R3A,MCM7 and PSKH1.

See also

References

Further reading