Breakage fusion bridge cycles

The Breakage-Fusion-Bridge (BFB) cycle is a mechanism of chromosomal instability that often results in chromosomal deletions, duplications, and complex rearrangements. It is typically triggered when a chromosome experiences a double-strand break (DSB), especially near the telomeric end, and fails to undergo proper repair.

The breakage-fusion-bridge (BFB) cycle is a mechanism of genomic instability that occurs during cell division, particularly when a chromosome end is broken or a telomere is lost. 

Here’s a step-by-step explanation of the mechanism of BFB in the context of chromosomal deletion:

Mechanism of the BFB Cycle

The BFB cycle is initiated by a double-strand break (DSB) in a chromosome, often near the telomere (the protective end of a chromosome). The key steps in the cycle are as follows:

Step 1: Chromosome Breakage

A chromosome undergoes a double-strand break at its end, which can occur due to telomere shortening, DNA damage, or mechanical stress during mitosis. If the telomere is lost or dysfunctional, the broken chromosome end is exposed and becomes “sticky.”

Step 2: End Fusion

Instead of undergoing proper DNA repair, the broken chromosome end fuses with another broken end. This can be either:

• Fusion with another broken chromatid from the same chromosome (sister chromatid fusion),
• Fusion with the broken end of a homologous chromosome or another non-homologous chromosome.

The fusion often results in a dicentric chromosome, which contains two centromeres.

Step 3: Bridge Formation During Mitosis

In the next mitotic division, the dicentric chromosome is pulled toward both poles by its two centromeres. This creates a chromatin bridge between the dividing daughter cells.

Step 4: Anaphase Bridge Breakage

The mechanical tension of the bridge causes it to break at a random point between the two centromeres. The broken ends lack telomeres and are again “sticky,” making them susceptible to further fusion in subsequent cell cycles.

Step 5: Cycle Repeats

The newly broken ends undergo another round of fusion, forming new dicentric chromosomes, and the cycle continues.

This cycle of breakage, fusion, and bridge formation creates a cascading series of chromosomal abnormalities, including deletions, duplications, inversions, and complex rearrangements.

Daughter Cell Consequences :

• eletion : One daughter cell receives a chromosome with a terminal deletion (a missing piece at the end). 
• Duplication : The other daughter cell receives a chromosome with a duplication, often in the form of an inverted repeat, at the end.