Molecular cytogenetics of the micronucleus: Still surprising

The purpose of this review is to provide an historical overview of the molecular cytogenetic approaches that have been pursed to identify the mechanism of origin of micronuclei as well as highlight the significance of the findings obtained for the understanding of the molecular action of harmful agents in the micronucleus assay. Then, we summarize recent exciting findings that have been obtained by applying molecular approaches to analyze the biology of micronuclei. These findings emphasize the role of micronuclei in the generation of genomic instability in the form of complex localized rearrangements characteristic of chromothripsis/chromoanagenesis, and put in evidence a fundamental and yet poorly understood aspect of the cell response to micronuclei: the activation of a cell-intrinsic innate immune response.