DNA replication factor CDT1

DNA Replication Factor CDT1 is a protein that plays a crucial role in the DNA replication process in eukaryotic cells. It is essential for the loading of the MCM (Minichromosome Maintenance) complex, a critical component of the pre-replication complex (pre-RC), onto DNA. This process is vital for the initiation of DNA replication.

Function

CDT1 works in conjunction with other proteins, including ORC, CDC6, and MCM, to ensure that DNA replication is initiated correctly at the replication origins. It specifically facilitates the recruitment of the MCM complex to the origins of replication, thereby enabling the unwinding of DNA and the subsequent recruitment of DNA polymerases for replication. The activity and availability of CDT1 are tightly regulated throughout the cell cycle to prevent re-replication, which can lead to genomic instability.

Regulation

The regulation of CDT1 is critical for maintaining genomic integrity. Several mechanisms are in place to control its activity, including:

• Proteolysis: CDT1 is subject to ubiquitin-mediated degradation, primarily through the action of the SCF complex and the CUL4-DDB1 complex in a process that is dependent on the cell cycle phase.
• Inhibition by Geminin: Geminin is a protein that directly binds to CDT1 and inhibits its function. This interaction prevents the re-loading of the MCM complex onto DNA after the initiation of replication, thus ensuring that replication occurs only once per cell cycle.
• Phosphorylation: CDT1 is also regulated by phosphorylation, which can affect its stability and interaction with other proteins.

Role in Cancer

Dysregulation of CDT1 has been implicated in the development of cancer. Overexpression of CDT1 can lead to re-replication and genomic instability, a hallmark of cancer cells. Consequently, CDT1 is considered a potential target for cancer therapy, and understanding its regulation and function could lead to the development of novel therapeutic strategies.

Research and Clinical Implications

Research on CDT1 continues to uncover its complex role in DNA replication and its implications for human health. Studies have explored its potential as a biomarker for cancer prognosis and as a target for therapeutic intervention. Inhibitors of CDT1, as well as strategies to modulate its activity, are being investigated for their potential to prevent or treat cancer by maintaining genomic stability.

See Also

• DNA replication
• Cell cycle
• Genomic instability
• Cancer