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

Mutagenesis
|December 18, 2010
PubMed

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.

Related Concept Videos

Additional Subnuclear Structures02:10

Additional Subnuclear Structures

The eukaryotic nucleus is a double membrane-bound organelle that contains nearly all of the cell’s genetic material in the form of chromosomes. It is rightly called the “brain” of the cell as it shoulders the responsibility of responding to various physiological processes, stress, altered metabolic conditions, and other cellular signals. 
The nucleus contains many membrane-less subnuclear organelles or nuclear bodies, such as nucleoli, Cajal bodies, speckles, paraspeckles, etc. These nuclear...
Microtubule Formation01:23

Microtubule Formation

Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation of...
Spindle Assembly02:50

Spindle Assembly

Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...
Meiosis I03:09

Meiosis I

Meiosis is the division of a diploid cell into haploid cells forming sperm and eggs in animals through differentiation. Meiosis I is the first stage of meiosis, where the genetic recombination of homologous chromosomes and the reduction of the ploidy level by half occurs.
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
The Nucleus01:25

The Nucleus

The nucleus is a membrane-bound organelle that acts as a control center in a eukaryotic cell. It contains chromosomal DNA, which controls gene expression and precisely regulates the production of proteins within the cell. In contrast, the DNA inside the mitochondria and chloroplast only carries out functions that are specific to those organelles.
Arrangement of DNA within Nucleus
The regulation of gene expression inside the nucleus is dependent on many factors, including the DNA structure. The...
Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...