MCMs in Cancer: Prognostic Potential and Mechanisms

Table 1

Summary of biological functions of the MCM subunits.

Subunit	Biological and functional significance	References
MCM2	Chaperones histones H3-H4.; Dephosphorylated by PTEN to restrict replication fork progression.; Phosphorylated by DDK at NTD terminus to activate pre-RC.; Interacts with Cdt1 at NTD to stabilize the coil structure.; Interacts with Cdc45 in the CMG complex at NTD.; Forms MCM2-5 gate for the MCM2-7 complex loading.	[9]; [10]; [11]; [4]; [12]; [13]
MCM3	Interacts with GINS component Psf2 in the CMG complex.; Interacts with and stimulates the ATPase activity of ORC·Cdc6 at CTD.	[12]; [14]
MCM4	Phosphorylated by DDK at NTD to activate pre-RC.; Interacts with Cdt1 at NTD to stabilize the coil structure.; Involved in translocation along single-stranded DNA in the MCM2-7 complex.	[11]; [4]; [1]
MCM5	Interacts with GINS component Psf3 in the CMG complex.; Interacts with Cdc45 in the CMG complex at NTD.; Forms MCM2-5 gate for the MCM2-7 complex loading.	[12]; [15]; [13]
MCM6	Phosphorylated by DDK at NTD terminus to activate pre-RC.; Interacts with Cdt1 at NTD to stabilize the coil structure.; Involved in translocation along single-stranded DNA in the MCM2-7 complex.	[11]; [4]; [1]; [1]
MCM7	Involved in translocation along single-stranded DNA in the MCM2-7.; Polyubiquitylated during replication termination.	[1]; [16]
MCM8	Functions as a helicase during replication elongation.; Stabilizes MCM9 and forms MCM8-9 complex to facilitate homologous recombination.	[17]; [18]
MCM9	Forms MCM8-9 complex to facilitate homologous recombination.; Functions in germ-line stem cells and tumor suppression.	[18]; [19]
MCM10	Functions as one of the initiation factors to activate the helicase activity of MCM2-7 complex.; Stabilizes Cdc45 and GINS association with Mcm2-7 and stimulates replication elongation.; Coordinates DNA helicase and polymerization activities during lagging strand synthesis.	[20]; [21]; [22]