Geminin

Protein involved in DNA replication

Geminin is a protein that plays a crucial role in the regulation of DNA replication and cell cycle progression. It is encoded by the GMNN gene in humans. Geminin functions primarily to inhibit the replication licensing factor Cdt1, thereby preventing re-replication of DNA within a single cell cycle.

Structure

Geminin is composed of 209 amino acids and has a molecular weight of approximately 25 kDa. The protein contains a coiled-coil domain that is essential for its function in inhibiting Cdt1.

Function

Geminin is involved in the regulation of DNA replication by inhibiting the activity of Cdt1, a protein necessary for the loading of the MCM complex onto DNA, which is a critical step in the initiation of DNA replication. By binding to Cdt1, Geminin prevents the re-replication of DNA, ensuring that the genome is replicated only once per cell cycle.

Regulation

The levels of Geminin are tightly regulated throughout the cell cycle. Geminin is absent during the G1 phase and accumulates during the S phase, G2 phase, and M phase. It is degraded by the anaphase-promoting complex/cyclosome (APC/C) during the transition from metaphase to anaphase, allowing Cdt1 to initiate a new round of DNA replication in the subsequent cell cycle.

Clinical Significance

Abnormal regulation of Geminin has been implicated in various types of cancer. Overexpression of Geminin can lead to genomic instability and has been observed in several malignancies, including breast cancer, colorectal cancer, and lung cancer.

Related Proteins

• Cdt1
• MCM complex
• Anaphase-promoting complex

See Also

• DNA replication
• Cell cycle
• Cancer