DNA replication initiation is a first step of genomic duplication. During initiation the ‘replisome' is assembled. Its core and engine, the CMG (Cdc45, MCM, GINs) helicase, is loaded onto the origins and activated. These events are promoted by the activity of DDK and S-CDK kinases. Previously, our lab identified new Mcm4 point mutants capable of supporting CMG helicase assembly in cells with dramatically reduced DDK activity through a suppressor screen. In this work, we tried to elucidate the exact region of Mcm4-NSD (N- terminal Serine/Threonine rich domain) responsible for inhibiting replication initiation and the molecular mechanism underlying the process. We found a conserved motif located between amino acids (aa) 134-138 of Mcm4-NSD. The elimination of this motif rescued cells in cdc7-4 ts or cdc7Δ backgrounds. The phenotype of mutants assessed by growth or spore viability assays confirmed the intrinsic inhibitory function within the proximal subdomain (aa 74-174) of Mcm4.