Breakage fusion bridge (BFB) in Meiosis

Meiosis is a specialized type of cell division that reduces the chromosome number by half and generates haploid gametes (sperm or eggs). During this process, homologous chromosomes pair and exchange genetic material through crossing over. A structural abnormality like an inversion or deletion can disrupt this pairing and result in abnormal chromosome segregation.

If a chromosome enters meiosis with a broken end (e.g., due to a terminal deletion or unprotected telomere), it may initiate a BFB cycle during or after meiosis I. The fusion of broken chromatids and subsequent bridge formation during anaphase can cause deletions, duplications, and chromosomal rearrangements in the resulting gametes.

2. Initiation of Meiotic BFB

Key Events Leading to Meiotic BFB:

• Terminal deletions or telomere loss on one or both chromatids.
• Inversion heterozygotes undergoing a single crossover within the inverted segment can lead to dicentric chromatids.
• Radiation-induced breaks in germ cells.
• Failure of telomere maintenance in early meiosis.

3. Mechanism of Meiotic BFB Cycle

Step-by-Step Process:

Step 1: Homologous Pairing and Crossing Over

• In prophase I of meiosis, homologous chromosomes align and undergo synapsis.
• If one homolog has a paracentric inversion (an inversion not including the centromere), and a crossover occurs within that inverted region, it results in:
  • One dicentric chromatid (with two centromeres).
  • One acentric fragment (no centromere).

Step 2: Anaphase I – Dicentric Bridge Formation

• During anaphase I, homologs segregate, but the dicentric chromatid is pulled toward both poles.
• This creates a chromatin bridge between the two daughter nuclei.
• The acentric fragment is lost because it cannot attach to the spindle apparatus.

Step 3: Bridge Breakage

• The dicentric bridge is subjected to mechanical tension and eventually breaks, usually at a random point between the centromeres.
• This break generates two chromatids with broken ends lacking telomeres.

Step 4: Fusion of Broken Ends

• During interkinesis (the short resting phase between meiosis I and II), the broken chromatids may fuse end-to-end, creating new dicentric chromosomes.
• The newly formed dicentric structures enter meiosis II.

Step 5: Anaphase II – Second Bridge and Break

• Similar to anaphase I, the dicentric chromatid is pulled toward opposite poles during meiosis II.
• This again leads to a bridge, which breaks, producing chromatids with new deletions and broken ends.

Step 6: Gamete Formation

• The final gametes produced may carry:
  • Terminal deletions (loss of gene-containing segments).
  • Duplications (from unequal segregation).
  • Complex rearrangements.