# Enhancing IDeA Research Partnerships in Oklahoma > **NIH NIH P20** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $136,645 ## Abstract Title: Deciphering the roles of Mcm10 and Polymerase epsilon interaction in maintaining genome stability. Abstract Maintenance of genome stability is key to cell survival. Defects in DNA replication and errors in the DNA damage response pathway contribute to genome instability. Replication stress is a leading cause of genome instability and occurs when replication forks progress slowly or stall. Intricate checkpoint pathways operate to ensure that the entry or progression through the S phase is blocked when the cells encounter DNA damage. Despite the importance of the checkpoint pathways, our understanding of how perturbed forks are sensed by the checkpoint and hence protected by the activated checkpoint remains far from complete. The long-term goal of our research is to address this lack of information by investigating the molecular interactions between the replication machinery and checkpoint pathways that govern checkpoint signaling and fork stabilization. DNA polymerase epsilon (Polε) and Minichromosome maintenance protein 10 (Mcm10) play important roles in replication, but issues related to these roles in replication remain to be resolved. In addition, there is no evidence that Mcm10 is involved in checkpoint activation. Our preliminary studies in budding yeast suggest that Mcm10 interacts with the essential, conserved C-terminal domain of Pol2 (catalytic subunit of Polε) and activates the checkpoint kinase at the perturbed forks. Here, we propose highly innovative ideas and experimental approaches to unambiguously establish the role of Mcm10 and Polε interaction in human cells at the damaged forks. Our first aim will focus on understanding how MCM10 and POLE1 interaction regulates replisome formation and fork progression during normal replication. This will help identify novel molecular mechanisms involved in DNA replication. The second aim will evaluate MCM10 and POLE1 interaction under DNA damaging conditions by studying checkpoint activation, replication competence, chromosomal aberrations, and DNA repair. Together, these proposed aims will resolve the outstanding issues related to the role of Mcm10 and Polε in DNA replication and checkpoint activation and thereby provide a holistic view of how they promote genome stability. The proposed research will involve a close collaboration between an INBRE investigator and a COBRE investigator and the integration of research with undergraduate education. In addition, this project will provide undergraduate students with the opportunity to learn current molecular biology techniques at a research-focused university. Relevance The aims of this proposal are to determine the roles of Mcm10 and Polε in DNA replication and checkpoint activation pathway. These studies will advance our understanding of how genome integrity is maintained over generations and how this integrity can be disrupted under stress in all eukaryotes. ## Key facts - **NIH application ID:** 10399034 - **Project number:** 3P20GM103447-22S1 - **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR - **Principal Investigator:** DARRIN R. AKINS - **Activity code:** P20 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $136,645 - **Award type:** 3 - **Project period:** 2001-09-06 → 2024-04-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10399034 ## Citation > US National Institutes of Health, RePORTER application 10399034, Enhancing IDeA Research Partnerships in Oklahoma (3P20GM103447-22S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399034. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*