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Archives of Toxicology

, Volume 90, Issue 11, pp 2657–2667 | Cite as

Impaired nuclear functions in micronuclei results in genome instability and chromothripsis

  • Mariona TerradasEmail author
  • Marta Martín
  • Anna GenescàEmail author
Review Article

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.

Keywords

Micronuclei Chromosome instability Chromatin bridges Chromothripsis DNA repair DNA replication 

Notes

Acknowledgments

The authors would like to apologize to those whose work has not been cited. We thank to Proof-Reading-Service.com for editing the manuscript. The Genome Integrity Group at Universitat Autònoma de Barcelona is supported by grants from Consejo de Seguridad Nuclear (CSN 2012-0001), EURATOM (Dark.Risk GA 323216) and Generalitat de Catalunya (2014-SGR-524).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Cell Biology Unit, Department of Cell Biology, Physiology and Immunology, Biosciences SchoolUniversitat Autònoma de BarcelonaBellaterraSpain

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