title: Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium.
abstract: 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.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK lpontel@mrc-lmb.cam.ac.uk kjp@mrc-lmb.cam.ac.uk.
authors.forename: Lucas B
authors.identifier: 0000-0001-8384-3422
authors.initials: LB
authors.lastname: Pontel
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Langenick
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.|Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville 41013, Spain.
authors.forename: Ivan V
authors.identifier: 0000-0001-7409-7341
authors.initials: IV
authors.lastname: Rosado
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.|Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford OX1 2HB, UK.
authors.forename: Xiao-Yin
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Traynor
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Kay
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK lpontel@mrc-lmb.cam.ac.uk kjp@mrc-lmb.cam.ac.uk.|Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QQ, UK.
authors.forename: Ketan J
authors.identifier: 0000-0001-8641-5802
authors.initials: KJ
authors.lastname: Patel
mesh_terms: D000595:Amino Acid Sequence; D004260:DNA Repair / Q000235:genetics; D004023:Dictyostelium / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D016296:Mutagenesis; D010587:Phagocytosis / Q000235:genetics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins
keywords: DNA repair; Dictyostelium; Mutagenesis; Phagocytosis; Xpf