After they have replicated, homologous chromosomes pair, synapse and recombine in meiotic prophase. These events ensure that chromosomes segregate properly to produce eggs and sperm with the correct number of chromosomes. We are interested in understanding how defects in these processes are monitored to make sure that they occur correctly and avoid the production of aneuploid gametes.
If chromosomes don’t synapse, they missegregate during meiosis and produce aneuploid eggs and sperm. We have shown that meiotic nuclei with unsynapsed chromosomes activate apoptosis (see Figure 1), indicating that a checkpoint monitors whether chromosomes have synapsed. We are further characterizing this meiotic checkpoint. Specifically, we want to know: 1) what signal is generated by unsynapsed chromosomes to activate this meiotic checkpoint; 2) how this signal is silenced during a normal meiosis; and 3) how this signal is transduced to promote apoptosis of defective nuclei. In mitosis, checkpoints have been shown to play an important role in genomic stability and preventing cancer. We predict that analysis of this meiotic checkpoint will reveal common mechanisms that contribute to maintaining genomic integrity and preventing aneuploidy.