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Causes and consequences of micronuclei

Journal

CURRENT OPINION IN CELL BIOLOGY
Volume 70, Issue -, Pages 91-99

Publisher

CURRENT BIOLOGY LTD
DOI: 10.1016/j.ceb.2021.01.004

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Funding

  1. US National Institutes of Health [R35-GM122476]
  2. Ludwig Institute for Cancer Research

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Micronuclei are small compartments with DNA content encapsulated by a nuclear envelope, found in cancers, during senescence, and after genotoxic stress. Compromised integrity of the micronuclear envelope disrupts DNA replication and repair, exposing micronuclear DNA to cytoplasm. Micronuclei play a central role in tumorigenesis, being a source of complex genome rearrangements and promoting a cellular immune response that may contribute to cancer metastasis.
Micronuclei are small membrane-bounded compartments with a DNA content encapsulated by a nuclear envelope and spatially separated from the primary nucleus. Micronuclei have long been linked to chromosome instability, genome rearrangements, and mutagenesis. They are frequently found in cancers, during senescence, and after genotoxic stress. Compromised integrity of the micronuclear envelope delays or disrupts DNA replication, inhibits DNA repair, and exposes micronuclear DNA directly to cytoplasm. Micronuclei play a central role in tumorigenesis, with micronuclear DNA being a source of complex genome rearrangements (including chromothripsis) and promoting a cyclic GMP-AMP synthase (cGAS)-mediated cellular immune response that may contribute to cancer metastasis. Here, we discuss recent findings on how micronuclei are generated, what the consequences are, and what cellular mechanisms can be applied to protect against micronucleation.

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