Grant: Project Grant

In this project, we will investigate two lesser-known members of the human APOBEC3 gene family, namely APOBEC3C and APOBEC3D. These genes produce proteins that play crucial roles in the body's defense against viruses. We recently demonstrated that APOBEC3C and APOBEC3D can cause mutations in the DNA of human cells, and surprisingly are important for the duplication of DNA that occurs when cells grow and divide. Mutations are typically detrimental, and cause many diseases, whereas the duplication of the DNA is essential for life. Thus, the functions of APOBEC3C and APOBEC3D present a conundrum whose solution will be relevant to understanding how genetic diseases arise. We have three objectives: 1. Identifying Mutation Sites: We will determine the specific locations in the genome where APOBEC3C and APOBEC3D cause mutations, to understand how they shape genome function. 2. Genetic Analysis: We will investigate the interactions of APOBEC3C and APOBEC3D to identify critical genes and pathways affected by APOBEC3C and APOBEC3D, and to understand their roles in DNA repair and DNA replication. 3. Understanding Replication Promotion: We will examine how APOBEC3C and APOBEC3D influence DNA replication by assessing their impact on replication efficiency and fidelity. We will investigate whether APOBEC3C and APOBEC3D are crucial for the integrity of the DNA replication process, especially under stress conditions. Our overall goal is to gain a comprehensive understanding of the roles played by APOBEC3C and APOBEC3D in genome mutation and DNA replication. Our findings will provide insights into when and where APOBEC3C and APOBEC3D mutate the human genome, and how the costs and benefits of APOBEC3C and APOBEC3D actions are balanced.