Causes and consequences of micronuclei

Ksenia Krupina; Alexander Goginashvili; Don W Cleveland

doi:10.1016/j.ceb.2021.01.004

Causes and consequences of micronuclei

Curr Opin Cell Biol. 2021 Jun:70:91-99. doi: 10.1016/j.ceb.2021.01.004. Epub 2021 Feb 18.

Authors

Ksenia Krupina¹, Alexander Goginashvili¹, Don W Cleveland²

Affiliations

¹ Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, 92093, USA; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, 92093, USA.
² Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, 92093, USA; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, 92093, USA. Electronic address: dcleveland@health.ucsd.edu.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Chromothripsis*
DNA Damage
Genomic Instability
Humans
Micronuclei, Chromosome-Defective*
Nuclear Envelope

Grants and funding

R35 GM122476/GM/NIGMS NIH HHS/United States