Essential to the survival of cellular life is proper replication and maintenance of the genome. Replication proteins Mcm10 and RecQ4 have well-characterized essential roles in assembly, initiation, and proper functioning of the eukaryotic replication machinery. Specifically, Mcm10 aids in the recruitment of Pol-α/primase as well as tethering the ssDNA stabilizing replication protein A (RPA) to the CMG complex, and RecQ4 delivers the GINS complex to the replication fork, which is essential for replication initiation. Past evidence suggests that Mcm10 is not required for RecQ4 chromatin localization or association with the CMG complex, conflicting with previous reports that Mcm10 mediates the interaction between RecQ4 and Mcm2-7 in an S-CDK dependent manner. A recent study demonstrated that truncating residues from the N-terminus (Sld2-like) domain of RecQ4 eliminated the Mcm10 interaction surface. We have found that a homozygous mutation of RecQ4 is lethal in fruit flies that do not also possess a C-terminal domain (CTD) truncation allele of Mcm10, suggesting that Mcm10’s RecQ4 interaction surface lies in the CTD of Mcm10. Additionally, we have used the Yeast Two-Hybrid System to demonstrate the interaction between Mcm10’s CTD and RecQ4. Specifically, our results indicate that the Mcm10-RecQ4 interaction is essential for high-stress replication states – like embryogenesis and endoreplication in larval salivary glands – but not for normal cell cycles. The Mcm10 CTD truncation rescue of lethal RecQ4 phenotypes can reveal much about how the cooperative roles of these proteins affect DNA replication, but this requires further investigation. Our research aims to explore the nature of the Mcm10-RecQ4 interaction by conducting genetic studies, protein interaction assays, stem cell proliferation analysis in the Drosophila ovary, and the generation of null Mcm10 and RecQ4 alleles using the CRISPR/Cas9 system. We propose that the Sld2-like domain of RecQ4 interacts with the CTD of Mcm10, mediating its associations with the replication fork and other replication factors like RPA and Ctf4.