title: Impaired nuclear functions in micronuclei results in genome instability and chromothripsis.
abstract: Micronuclei (MN) have generally been considered a consequence of DNA damage and, as such, have been used as markers of exposure to genotoxic agents. However, advances in DNA sequencing methods and the development of high-resolution microscopy with which to analyse chromosome dynamics in live cells have been fundamental in building a more refined view of the existing links between DNA damage and micronuclei. Here, we review recent progress indicating that defects of micronuclei affect basic nuclear functions, such as DNA repair and replication, generating massive damage in the chromatin of the MN. In addition, the physical isolation of chromosomes within MN offers an attractive mechanistic explanation for chromothripsis, a massive local DNA fragmentation that produces complex rearrangements restricted to only one or a few chromosomes. When micronuclear chromatin is reincorporated in the daughter cell nuclei, the under-replicated, damaged or rearranged micronuclear chromatin might contribute to genome instability. The traditional conception of micronuclei has been overturned, as they have evolved from passive indicators of DNA damage to active players in the formation of DNA lesions, thus unravelling previously unforeseen roles of micronuclei in the origins of chromosome instability.
authors.affiliation: Cell Biology Unit, Department of Cell Biology, Physiology and Immunology, Biosciences School, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain. mariona.terradas@uab.es.
authors.forename: Mariona
authors.initials: M
authors.lastname: Terradas
authors.affiliation: Cell Biology Unit, Department of Cell Biology, Physiology and Immunology, Biosciences School, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martín
authors.affiliation: Cell Biology Unit, Department of Cell Biology, Physiology and Immunology, Biosciences School, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain. anna.genesca@uab.es.
authors.forename: Anna
authors.initials: A
authors.lastname: Genescà
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000072837:Chromothripsis / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D042822:Genomic Instability / Q000187:drug effects*; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D008954:Models, Biological; D009153:Mutagens / Q000633:toxicity*; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D009153:Mutagens
keywords: Chromatin bridges; Chromosome instability; Chromothripsis; DNA repair; DNA replication; Micronuclei