Functional Characterization of POLE1 Variant Fibroblasts Reveals Replication Stress and Increased Sensitivity to Genotoxic Stress

Collectively, these findings provide the first functional characterization of a patient-derived <i>POLE1</i>-variant fibroblast cell line and indicate that altered Pol ε function may influence cellular responses to genotoxic stress. While based on primary fibroblasts from a single compound-heterozygous patient, validation in additional patient-derived or isogenic models will be required to determine the broader relevance of these findings.