Regulation of Anaphase Progression during Caenorhabditis elegans Oocyte Meiosis

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Meiosis is a specialized form of cell division where chromosomes are duplicated once and segregated twice, in order to reduce the chromosome number by half to generate haploid gametes. In contrast to mitosis, oocyte meiosis in many species occurs in the absence of centrosomes, the microtubule organizing centers that nucleate microtubules and help to define the spindle poles. We have used C. elegans oocytes as a model system to study the mechanisms by which chromosomes congress and segregate on these acentrosomal spindles. ', 'C. elegans oocytes use a chromosome segregation mechanism that is independent of end-on kinetochore microtubule attachments and instead utilizes lateral attachments and depends on a complex of proteins containing AIR-2/Aurora B kinase that forms a ring around the center of each homologous chromosome pair (Ring Complex, RC). These RCs facilitate congression during metaphase and then are released from chromosomes in anaphase and progressively disassemble as the chromosomes segregate. In this dissertation, we first demonstrate that RC disassembly and other aspects of normal anaphase progression are delayed in response to a variety of meiotic errors, revealing a regulatory mechanism for anaphase progression as well as a novel checkpoint-like mechanism that may function to allow errors more time to resolve. Next, we uncover mechanisms underlying the dynamic regulation of the RCs, revealing a general strategy by which protein complexes can be progressively remodeled. We find that the stability of the RC is regulated by a balance of SUMOylation and deSUMOylation activity and that the SUMO protease ULP-1 enables RC disassembly during anaphase. Finally, we provide further evidence that these unique chromosome segregation mechanisms function in the context of stabilized lateral microtubule attachments that persist through anaphase. These findings contribute to the overall understanding of cellular checkpoints, anaphase progression, and protein complex regulation during dynamic cellular processes.

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  • 10/28/2019
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