MCM10 Activators

Chemical activators of MCM10 function by inducing cellular states that necessitate the activation of the protein's replication functions. Aphidicolin and Hydroxyurea create replication stress by inhibiting DNA polymerase and depleting deoxyribonucleotide pools, respectively. This stress can activate MCM10 as the cell mobilizes its replication machinery to stabilize and maintain the integrity of the replication forks. DNA topoisomerase inhibitors like Camptothecin and Etoposide introduce replication fork stalling and double-strand breaks, which can also lead to the activation of MCM10. The protein's role in the DNA damage response is vital for facilitating replication restart and overcoming these stressors.

Additional compounds, such as Caffeine and specific kinase inhibitors (VE-821, Roscovitine, PF-00477736, KU-55933), disrupt the normal replication checkpoint controls by inhibiting ATM and ATR kinases or cyclin-dependent kinases (CDKs) and checkpoint kinase 1 (Chk1). This disruption can result in an increased demand for MCM10 activity as the cells attempt to continue DNA replication without the full support of normal checkpoint functions. Gemcitabine, MK-8776, and UCN-01 further contribute to replication stress by incorporating nucleoside analogs or inhibiting proteins involved in replication fork progression. Such environmental conditions within the cell can stimulate the functional activation of MCM10, as it becomes a crucial component in the response to replication stress and the maintenance of replication fork integrity.