meiotic recombination checkpoint signaling

Definition

Target type: biologicalprocess

A signaling process that contributes to a meiotic recombination checkpoint, that acts during late prophase I (pachytene) and prevents segregation of homologous chromosomes until recombination is completed, ensuring proper distribution of the genetic material to the gametes. [PMID:14718568]

Meiotic recombination checkpoint signaling is a crucial process that ensures proper chromosome segregation during meiosis, the specialized cell division that produces gametes (sperm and egg cells). It involves a complex interplay of proteins and signaling pathways that monitor the progression of meiotic recombination, a process where homologous chromosomes exchange genetic material. This exchange is essential for proper chromosome pairing and segregation.

The checkpoint monitors several key events during recombination, including:

1. **Double-strand break (DSB) formation:** Meiotic recombination begins with the creation of DSBs in the DNA, which are then repaired using the homologous chromosome as a template.
2. **DSB repair by homologous recombination:** The DSBs are repaired through a series of steps involving strand invasion, DNA synthesis, and resolution, ultimately leading to the formation of crossovers (chiasmata) that physically link homologous chromosomes.
3. **Formation of crossover intermediates:** Intermediate structures like Holliday junctions are formed during recombination, which are eventually resolved to create crossovers.

If any of these steps are disrupted or delayed, the checkpoint system triggers a delay in cell cycle progression, allowing time for repair or for the cell to activate an apoptotic pathway if the damage is irreparable.

**Key proteins involved in the meiotic recombination checkpoint:**

* **Spo11:** A protein responsible for creating DSBs.
* **Mre11, Rad50, Nbs1 (MRN complex):** A complex involved in processing DSBs.
* **ATM (Ataxia telangiectasia mutated):** A protein kinase that senses DNA damage and activates downstream signaling pathways.
* **ATR (Ataxia telangiectasia and Rad3-related):** Another protein kinase involved in DNA damage response, particularly for single-stranded DNA.
* **Chk1 and Chk2:** Downstream kinases that are activated by ATM and ATR and mediate cell cycle arrest.
* **RecA (in bacteria), Rad51 (in eukaryotes):** Proteins involved in homologous recombination.

**Mechanism of checkpoint signaling:**

1. **DNA damage recognition:** Upon DSB formation, the MRN complex and other DNA repair proteins are recruited to the site of damage.
2. **ATM/ATR activation:** ATM and ATR are activated upon sensing the DSB or other DNA damage.
3. **Chk1/Chk2 phosphorylation:** ATM and ATR phosphorylate Chk1 and Chk2, activating these kinases.
4. **Cell cycle arrest:** Activated Chk1 and Chk2 phosphorylate key cell cycle regulators, such as Cdc25 and Wee1, leading to a delay in cell cycle progression.

**Consequences of checkpoint failure:**

* **Aneuploidy:** Incorrect chromosome segregation during meiosis can lead to aneuploidy, a condition where cells have an abnormal number of chromosomes.
* **Infertility:** Aneuploidy in gametes can cause infertility or developmental problems in offspring.
* **Cancer:** Meiotic recombination defects can contribute to the accumulation of mutations that can drive cancer development.

Meiotic recombination checkpoint signaling is a critical process that safeguards the integrity of the genome during meiosis. Its intricate network of proteins and signaling pathways ensures that recombination proceeds correctly, resulting in healthy gametes and offspring.'"

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