Cdt1

Cdt1

Cdt1 (Chromatin licensing and DNA replication factor 1) is a crucial protein involved in the regulation of DNA replication in eukaryotic cells. It plays a significant role in ensuring that the genome is replicated precisely once per cell cycle, thus maintaining genomic stability.

Function

Cdt1 is a key component of the pre-replication complex (pre-RC), which assembles at the origins of replication during the G1 phase of the cell cycle. It works in conjunction with other proteins such as Cdc6 and the origin recognition complex (ORC) to load the MCM complex (minichromosome maintenance complex) onto DNA, a critical step in the initiation of DNA replication.

Regulation

The activity of Cdt1 is tightly regulated to prevent re-replication of DNA within a single cell cycle. This regulation is achieved through several mechanisms:

• Proteolysis: Cdt1 is targeted for degradation by the ubiquitin-proteasome system during the S phase and G2 phase of the cell cycle. This degradation is mediated by the SCF complex and the CRL4 complex, which ubiquitinate Cdt1, marking it for destruction.

• Inhibition by Geminin: Cdt1 is also inhibited by the protein Geminin, which binds to Cdt1 and prevents it from loading the MCM complex onto DNA. Geminin levels are high during the S, G2, and M phases, ensuring that Cdt1 is inactive during these phases.

• Phosphorylation: Cdt1 can be phosphorylated by various kinases, which can alter its activity and stability.

Clinical Significance

Dysregulation of Cdt1 can lead to genomic instability, which is a hallmark of cancer. Overexpression of Cdt1 has been observed in several types of cancer, and it is thought to contribute to oncogenesis by promoting DNA re-replication and genomic instability. Conversely, loss of Cdt1 function can lead to cell cycle arrest and apoptosis.

Research

Ongoing research is focused on understanding the precise molecular mechanisms by which Cdt1 is regulated and how its dysregulation contributes to disease. There is also interest in targeting the Cdt1 regulatory pathway for cancer therapy.

See Also

• DNA replication
• Cell cycle
• Geminin
• MCM complex

External Links

• Cdt1 Gene - NCBI
• Cdt1 Protein - UniProt