A proliferating cell must grow, duplicate, and divide. Faithful duplication of DNA is required to pass the genetic information to the daughter cell. DNA replication is a fundamental process that frequently encounters challenges from exogenous and endogenous sources. Barriers to replication slow down DNA synthesis and threaten the genetic integrity and viability of the cell. Cells are equipped with specialized proteins called kinases that overcome replication barriers by mounting robust molecular signaling responses. Kinases phosphorylate hundreds of proteins that halt cellular processes, facilitate the removal of replication barriers, and promote genomic stability. Kinase mediated signaling ensures that errors with DNA are fixed before cell division.Kinases present only one side of the coin. Persistent kinase signaling can permanently inhibit cellular processes and result in cell death. Hence, once the barrier has been removed, kinase signaling must be turned off. Phosphatases are specialized proteins that counteract kinase signaling. They dephosphorylate proteins, facilitating DNA synthesis and resumption of other normal cellular processes. Though phosphatases are expected to be crucial for cell viability and proliferation, very little is known about them. My thesis explores this fundamental question of the role of phosphatases in the recovery from replication stress. Previous studies employed low-throughput approaches and identified a few key phosphatases that can dephosphorylate other proteins. I utilized high-throughput phosphoproteomics to investigate the contribution of phosphatases to the global signaling response. I found a phosphatase of the PP2C family called PPM1D (also known as PP2Cδ and Wip1) to be an important regulator of hydroxyurea induced replication stress. PPM1D negatively regulates kinase signaling by dephosphorylating many DNA replication and repair associated proteins. One such protein called RAP80 is a direct target of PPM1D. I demonstrate that PPM1D dephosphorylates RAP80 that triggers a change in a key replication protein called RAD51 promoting DNA synthesis. Specifically, PPM1D-RAP80 alters the association of RAD51 with DNA thereby controlling DNA replication until the barrier has been removed. In summary, I identified and characterized the role of PPM1D in promoting replication restart during the recovery from hydroxyurea induced replication stress. Mechanistically, I show that PPM1D dephosphorylates RAP80 thereby allowing RAD51 to associate with the chromatin. This subsequently facilitates RAD51 mediated homologous recombination and replication restart. My work uncovers a novel molecular signaling processes that enables DNA replication at the fork post replication stress. My work highlights a novel phosphorylation based signaling circuit that regulates DNA replication dynamics during replication stress recovery. This sheds light on the identity and function of the previously obscure phosphatases in this pathway. Lastly, I discovered a novel role for RAP80, a canonical double strand break repair protein, in regulating DNA replication. Overall, my PhD research uncovers an important signaling network and opens several new avenues of research. It serves as a platform to investigate the roles of other phosphatases and discover alternative roles for the PPM1D-RAP80-RAD51 signaling pathway. PPM1D could also make a potential chemotherapeutic target in cancers that display high levels of replication stress.