RT Journal Article T1 Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium A1 Pontel, Lucas B. A1 Langenick, Judith A1 Rosado, Ivan V. A1 Zhang, Xiao-Yin A1 Traynor, David A1 Kay, Robert R. A1 Patel, Ketan J. K1 Xpf K1 Phagocytosis K1 Mutagenesis K1 Dictyostelium K1 DNA repair K1 Dna-damage K1 Discoideum K1 Bacteria K1 Resistance K1 Repair K1 Methanol K1 Pathway K1 Growth K1 Genes K1 Ameba AB As time passes, mutations accumulate in the genomes of all living organisms. These changes promote genetic diversity, but also precipitate ageing and the initiation of cancer. Food is a common source of mutagens, but little is known about how nutritional factors cause lasting genetic changes in the consuming organism. Here, we describe an unusual genetic interaction between DNA repair in the unicellular amoeba Dictyostelium discoideum and its natural bacterial food source. We found that Dictyostelium deficient in the DNA repair nuclease Xpf (xpf-) display a severe and specific growth defect when feeding on bacteria. Despite being proficient in the phagocytosis and digestion of bacteria, over time, xpf(-) Dictyostelium feeding on bacteria cease to grow and in many instances die. The Xpf nuclease activity is required for sustained growth using a bacterial food source. Furthermore, the ingestion of this food source leads to a striking accumulation of mutations in the genome of xpf(-) Dictyostelium. This work therefore establishes Dictyostelium as a model genetic system to dissect nutritional genotoxicity, providing insight into how phagocytosis can induce mutagenesis and compromise survival fitness. PB Company of biologists ltd SN 0021-9533 YR 2016 FD 2016-12-15 LK http://hdl.handle.net/10668/19141 UL http://hdl.handle.net/10668/19141 LA en DS RISalud RD Apr 7, 2025