Fate of micronuclei and micronucleated cells.
The present review describes available evidence about the fate of micronuclei and micronucleated cells. Micronuclei are small, extranuclear chromatin bodies surrounded by a nuclear envelope. The mechanisms underlying the formation of micronuclei are well understood but not much is known about the potential fate of micronuclei and micronucleated cells. Many studies with different experimental approaches addressed the various aspects of the post-mitotic fate of micronuclei and micronucleated cells. These studies are reviewed here considering four basic possibilities for potential fates of micronuclei: degradation of the micronucleus or the micronucleated cell, reincorporation into the main nucleus, extrusion from the cell, and persistence in the cytoplasm. Two additional fates need to be considered: premature chromosome condensation/chromothripsis and the elimination of micronucleated cells by apoptosis, yielding six potential fates for micronuclei and/or micronucleated cells. The available data is still limited, but it can be concluded that degradation and extrusion of micronuclei might occur in rare cases under specific conditions, reincorporation during the next mitosis occurs more frequently, and the majority of the micronuclei persist without alteration at least until the next mitosis, possibly much longer. Overall, the consequences of micronucleus formation on the cellular level are still far from clear, but they should be investigated further because micronucleus formation may contribute to the initial and later steps of malignant cell transformation, by causing gain or loss of genetic material in the daughter cells and by the possibility of massive chromosome rearrangement in chromosomes entrapped within a micronucleus by the mechanisms of chromothripsis and chromoanagenesis.
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Germany; Bavarian Health and Food Safety Authority, Erlangen, Germany. Electronic address: Hintzsche@toxi.uni-wuerzburg.de.
Henning
H
Hintzsche
Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
Ulrike
U
Hemmann
Dr. Knoell Consult, Mannheim, Germany.
Albrecht
A
Poth
Merck KGaA, Darmstadt, Germany.
Dietmar
D
Utesch
Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
Jasmin
J
Lott
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Germany.
Helga
H
Stopper
D000818:Animals; D002460:Cell Line; D006801:Humans; D048631:Micronucleus, Germline
Functional properties; Genomic instability; Micronucleated cells; Micronuclei; Postmitotic fate