Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins

MCM2-7, a complex of six subunits, is an essential component of the prerepl ication chromatin that is assembled at Saccharomyces cerevisiae replication origins during G(1) phase. It is also believed to be the processive helica se at growing forks. To elucidate the action of MCM2-7 during the transitio n from initiation to elongation replication, we have focused our studies on Mcm(10), a replication initiation protein that physically interacts with m embers of the MCM2-7 complex. We show that Mcm10 is a chromatin-associated protein that mediates the association of the MCM2-7 complex with replicatio n origins. Furthermore, diminished interaction between Mcm10 and Mcm7, a su bunit of the MCM2-7 complex, by a mutation in either Mcm10 or Mcm7 inhibits replication initiation. Surprisingly, a double mutant containing both the mcm10-1 and mcm7-1 (cdc47-1) alleles restores interaction between Mcm10 and Mcm7 and corrects all of the defects exhibited by each of the single mutan ts, including the stalling of replication forks at replication origins typi cally seen in mcm10-1 cells. This mutual compensation of defects between tw o independently isolated mutations is allele specific. These results sugges t that Mcm10, like Mcm7, is a critical component of the prereplication chro matin and that interaction between Mcm10 and Mcm7 is required for proper re plication initiation and prompt release of origin-bound factors.