Mcm10 proteolysis initiates before the onset of M-phase.

Background: Mcm10 protein is essential for initiation and elongation phases of replication. Human cells proteolyze Mcm10 during mitosis, presumably to ensure a single round of replication. It has been proposed that anaphase promoting complex ubiquitinates Mcm10 in late M and early G1 phases.

Results: In contrast to the previous work, we report that the degradation of Mcm10 is initiated at the onset of mitosis. Immunoblotting and immunofluorescence assays display that Mcm10 levels are low in all phases of mitosis. We report that Mcm10 degradation is not dependent on anaphase promoting complex. Further, the proteolysis in M-phase can be independently mediated by non-overlapping regions of Mcm10, apparently employing a redundant mechanism to ensure downregulation.

Conclusions: It is believed that the proteolysis of Mcm10 during mitosis is a vital mechanism to prevent aberrant initiation of replication and the present study describes the regulation of Mcm10 during this phase of the cell-cycle.