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Regulation of Meiotic Synapsis in C. elegans

  • Author(s): Bohr, Tisha Emily
  • Advisor(s): Bhalla, Needhi
  • et al.
Abstract

Defects in chromosome segregation during cellular division can lead to daughter cells with the incorrect number of chromosomes. This is associated with cancer progression in mitotically dividing cells and birth defects and infertility in meiotically dividing cells. Therefore, cell cycle checkpoints are in place to monitor key events in order to reduce the probability of aberrant cell divisions. Synapsis involves the assembly of a proteinaceous structure, the synaptonemal complex (SC), between paired homologous chromosomes and is essential for proper meiotic chromosome segregation. In C. elegans, the synapsis checkpoint selectively removes nuclei with unsynapsed chromosomes. This checkpoint depends on Pairing Centers (PCs), cis- acting sites that promote pairing and synapsis by interacting with the nuclear envelope to access cytoplasmic microtubules. The spindle assembly checkpoint (SAC) monitors microtubule attachment at kinetochores during metaphase and also uses cis-acting sites, centromeres, as platforms for activation. These similarities led us to hypothesize that SAC proteins might also be required for the synapsis checkpoint. Here, I show that some SAC components are required to negatively regulate synapsis and promote the synapsis checkpoint response. These proteins require full PC function to inhibit synapsis, suggesting a role at PCs. These data support a model in which SAC proteins monitor the stability of pairing, between homologues to regulate synapsis and elicit a checkpoint response. I also show that SC components are required for a functional synapsis checkpoint. Mutation of these components does not abolish PC function, indicating they are bonafide checkpoint components. These data suggest that, in addition to homolog pairing, SC assembly may be monitored by the synapsis checkpoint. These findings are important in understanding conserved mechanisms that allow cells to maintain genomic integrity and lend insight into preventing human tumorigenesis, birth defects and infertility.

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