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Updated: Jun 5, 2026

The Micronucleus Assay on Cryopreserved Whole Blood
Published on: February 23, 2024
Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells
M Fenech1, M Kirsch-Volders, A T Natarajan
1Department of Nutritional Genomics and DNA Damage Diagnostics, Commonwealth Scientific and Industrial Research Organisation Food and Nutritional Sciences, Gate 13 Kintore Avenue, PO Box 10041, Adelaide BC, South Australia 5000, Australia. michael.fenech@csiro.au
Abstract:
Micronuclei (MN) and other nuclear anomalies such as nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) are biomarkers of genotoxic events and chromosomal instability. These genome damage events can be measured simultaneously in the cytokinesis-block micronucleus cytome (CBMNcyt) assay. The molecular mechanisms leading to these events have been investigated over the past two decades using molecular probes and genetically engineered cells. In this brief review, we summarise the wealth of knowledge currently available that best explains the formation of these important nuclear anomalies that are commonly seen in cancer and are indicative of genome damage events that could increase the risk of developmental and degenerative diseases. MN can originate during anaphase from lagging acentric chromosome or chromatid fragments caused by misrepair of DNA breaks or unrepaired DNA breaks. Malsegregation of whole chromosomes at anaphase may also lead to MN formation as a result of hypomethylation of repeat sequences in centromeric and pericentromeric DNA, defects in kinetochore proteins or assembly, dysfunctional spindle and defective anaphase checkpoint genes. NPB originate from dicentric chromosomes, which may occur due to misrepair of DNA breaks, telomere end fusions, and could also be observed when defective separation of sister chromatids at anaphase occurs due to failure of decatenation. NBUD represent the process of elimination of amplified DNA, DNA repair complexes and possibly excess chromosomes from aneuploid cells.
Insights
Micronuclei (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) are key biomarkers for genotoxicity and genome instability. Understanding their formation mechanisms is crucial for assessing disease risk.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Micronuclei (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) are nuclear anomalies indicating genotoxic events and chromosomal instability.
- These biomarkers are crucial for assessing genome damage, which is linked to cancer and other diseases.
- The cytokinesis-block micronucleus cytome (CBMNcyt) assay allows simultaneous measurement of these anomalies.
Purpose of the Study:
- To review and summarize current knowledge on the molecular mechanisms behind the formation of MN, NPBs, and NBUDs.
- To elucidate how these nuclear anomalies arise from specific genotoxic events and cellular processes.
- To highlight the significance of these biomarkers in the context of cancer and disease risk.
Main Methods:
- Review of existing literature over the past two decades.
- Analysis of molecular probes and genetically engineered cell data.
- Synthesis of findings related to DNA damage, chromosome segregation, and nuclear anomalies.
Main Results:
- Micronuclei formation is linked to lagging chromosome/chromatid fragments or whole chromosome missegregation.
- Nucleoplasmic bridges arise from dicentric chromosomes or defective sister chromatid separation.
- Nuclear buds are associated with the elimination of amplified DNA or excess chromosomes.
Conclusions:
- The formation of MN, NPBs, and NBUDs involves complex molecular mechanisms related to DNA damage and chromosome dynamics.
- These nuclear anomalies serve as critical indicators of genome instability and potential disease risk.
- Continued research into these mechanisms aids in understanding cancer development and other degenerative diseases.
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