Impaired nuclear functions in micronuclei results in genome instability and chromothripsis

Mariona Terradas, Marta Martín, Anna Genescà

Research output: Contribution to journalReview articleResearchpeer-review

30 Citations (Scopus)

Abstract

© 2016, Springer-Verlag Berlin Heidelberg. 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.
Original languageEnglish
Pages (from-to)2657-2667
JournalArchives of Toxicology
Volume90
Issue number11
DOIs
Publication statusPublished - 1 Nov 2016

Keywords

  • Chromatin bridges
  • Chromosome instability
  • Chromothripsis
  • DNA repair
  • DNA replication
  • Micronuclei

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