title: Bacterial genotoxins: The long journey to the nucleus of mammalian cells.
abstract: Bacterial protein genotoxins target the DNA of eukaryotic cells, causing DNA single and double strand breaks. The final outcome of the intoxication is induction of DNA damage responses and activation of DNA repair pathways. When the damage is beyond repair, the target cell either undergoes apoptosis or enters a permanent quiescent stage, known as cellular senescence. In certain instances, intoxicated cells can survive and proliferate. This event leads to accumulation of genomic instability and acquisition of malignant traits, underlining the carcinogenic potential of these toxins. The toxicity is dependent on the toxins' internalization and trafficking from the extracellular environment to the nucleus, and requires a complex interaction with several cellular membrane compartments: the plasma membrane, the endosomes, the trans Golgi network and the endoplasmic reticulum, and finally the nucleus. This review will discuss the current knowledge of the bacterial genotoxins internalization pathways and will highlight the issues that still remain unanswered. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.
authors: Dept. Cell and Molecular Biology, Karolinska Institutet, Box 285, S-171 77 Stockholm, Sweden. Electronic address: Teresa.Frisan@ki.se.
authors: Teresa
authors: T
authors: Frisan
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism* / Q000472:pathogenicity; D001424:Bacterial Infections / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016922:Cellular Senescence; D004249:DNA Damage; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D009153:Mutagens / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D009153:Mutagens
keywords: Bacterial genotoxins; Cytolethal distending toxin; Endoplasmic reticulum; Intracellular trafficking; Lipid rafts; Nucleus; Retrograde transport; Toxin receptor; Trans Golgi network; Typhoid toxin