Chromatin bridge

The faithful inheritance of genetic information from one cellular generation to the next heavily relies on the duplication of deoxyribonucleic acid (DNA), as well as the formation of two identical daughter cells. This complicated cellular process, known as mitosis, depends on a multitude of cellular checkpoints, signals, interactions and signal cascades for accurate and faithful functioning. Cancer, characterized by uncontrollable cell growth mechanisms and high tendencies for proliferation and metastasis, is highly prone to mitotic mistakes. As a result, several forms of chromosomal aberrations occur, including, but not limited to, binucleated cells, multipolar spindles and micronuclei.[3] Chromatin bridges may serve as a marker of cancer activity.

A. Microtubules localized at a chromatin bridge. These polymers are stained with anti-tubulin antibody and viewed using fluorescence microscopy. B. Merged images of two daughter cells connected by a chromatin bridge. The fluorescence techniques of indirect immunofluorescence and DAPI staining were utilized. C. The same cells visualized using DAPI staining.

Chromatin bridges may form by any number of processes wherein chromosomes remain topologically entangled during mitosis. One way in which this may occur is the failure to resolve joint molecules formed during homologous recombination mediated DNA repair, a process that ensures that replicated chromosomes are intact before chromosomes are segregated during cell division. In particular, genetic studies have demonstrated that the loss of the enzymes BLM (Bloom's Syndrome Helicase) or FANCM each result in a dramatic increase in the number of chromatin bridges. This occurs because loss of these genes causes an increase in chromosome fusions, either in an end-to-end manner or through topological entrapment (e.g., catenation or unresolved DNA cross-links), have also been associated with chromatin bridge formation. When viewed under a fluorescence microscope and immunostained for cytological markers, these chromatin bridges appear to emanate from either centromeres, telomeres or DNA crosslinks (as marked by FANCD2).[4]

A chromatin bridge, visualized using DAPI staining.

Chromatin bridges can be viewed utilizing a laboratory technique known as fluorescence microscopy. Fluorescence is the process that involves excitation of a fluorophore (a molecule with the ability to emit fluorescent light in the visible light spectrum) using ultraviolet light. After the fluorophore becomes chemically excited by the presence of UV light, it emits visible light at a specific wavelength, producing different colors. Fluorophores may be added as a molecular tag to different portions of a cell. DAPI is a fluorophore that specifically binds to DNA and fluoresces blue. In addition, immunofluorescence may be used as a laboratory technique to tag cells with specific fluorophores using antibodies, immune proteins created by B lymphocytes. Antibodies are utilized by the immune system in the identification and binding of foreign substances. Tubulin is a monomer of microtubules that compose the cellular cytoskeleton. The antibody anti-tubulin specifically binds to these tubulin monomeric subunits. A fluorophore can be chemically attached to the anti-tubulin antibody, which then fluoresces green. Numerous antibodies may bind to microtubules in order to amplify the fluorescent signal. Fluorescence microscopy allows for the observation of different components of the cell against a dark background for high intensity and specificity.