Geminin is a protein that inhibits the initiation of DNA replication by binding to and inhibiting the activity of Cdt1, a licensing factor necessary for the formation of the pre-replicative complex (pre-RC). The pre-RC is essential for the initiation of DNA replication, and its formation is tightly regulated to prevent re-replication of the genome within a single cell cycle.
During the G1 phase of the cell cycle, Cdt1 binds to the origin recognition complex (ORC) and Cdc6, facilitating the loading of the MCM2-7 helicase complex onto DNA, which is a critical step in the formation of the pre-RC. Geminin inhibits this process by binding to Cdt1, preventing it from interacting with the ORC and Cdc6, thereby blocking the loading of the MCM2-7 complex .
The activity of Geminin is regulated by the cell cycle. It is present during the S, G2, and M phases, where it inhibits the reformation of the pre-RC, thus preventing re-replication. At the metaphase-anaphase transition, Geminin is targeted for degradation by the anaphase-promoting complex (APC), allowing the formation of new pre-RCs in the subsequent G1 phase .
Geminin has been studied extensively for its role in cancer biology. Overexpression of Geminin has been observed in various types of cancers, and it is thought to contribute to the uncontrolled proliferation characteristic of cancer cells. As such, Geminin is considered a potential target for cancer therapy .
Recombinant Geminin refers to the protein produced through recombinant DNA technology, which involves inserting the gene encoding Geminin into an expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant protein can be used in various research applications, including studies on DNA replication, cell cycle regulation, and cancer biology .
Recombinant Geminin is widely used in research to study its interactions with other proteins involved in DNA replication and cell cycle regulation. It is also used in assays to investigate the mechanisms by which Geminin inhibits the formation of the pre-RC and to screen for potential inhibitors that could be used in cancer therapy .