This $2,285,694 project grant from the National Science Foundation's Biological Sciences program (CFDA 47.074) supports research at Tufts University to study the relationship between DNA replication and tandem repeat instability. The grantee will combine genetic assays and single-cell live microscopy analysis in a model system to understand how repeat length changes during replication. This dual approach will examine how a repeat's length, propensity to form DNA structures, and orientation relative to replication direction affect the progression of the replication fork. A focus is on the role of coupling between leading and lagging strand syntheses and dNTP pool complexity in repeat instability. The research seeks to provide fundamental insights into mechanisms of DNA repeat expansions, which are associated with over 50 hereditary human diseases. The award period is from July 15, 2022 through June 30, 2026.