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Abstract:
Meiosis is specialized cell division that is essential to cut in half the number of chromosomes in a cell for sexual reproduction. In C. elegans, specific chromosome regions called Pairing Centers, are required for proper meiotic segregation. These regions were identified through genetic analysis of chromosome rearrangements. I contributed to work from our lab that demonstrated that these regions have two separable activities: they stabilize homolog pairing and directly promote synapsis. My subsequent work has uncovered essential cis- and trans-acting components that contribute to Pairing Center function. We first identified HIM-8 as a protein required specifically for X chromosome pairing and synapsis. (Chapter 1) HIM-8 localizes to the X chromosome Pairing Center and the nuclear envelope during early meiosis. him-8 mutations have no discernible effect on the segregation behavior of any of the autosomes. him-8 is located in an unusual operon containing three additional genes with high homology to him-8 and each other, which I have named zim-1, zim-2, and zim-3 (for zinc finger in meiosis ). I subsequently demonstrated analogous roles for ZIM-1, ZIM-2, and ZIM-3 at the autosomal Pairing Centers through mutational analysis and immunolocalization (Chapter 2). In addition, I have identified and carried out comparative analysis of orthologs of ZIM/HIM-8 family in related nematodes. C. remanei, like C. elegans, has four members of this protein family, but C. briggsae, has five, indicating recent expansion and/or contraction of this cluster. Finally, I have identified a family of short, repetitive sequence elements that recruit HIM-8 and the ZIM proteins to the Pairing Center regions of chromosomes (Chapter 3). This group of genes encodes the first chromosome-specific proteins implicated in homolog pairing and synapsis. Analysis of this family of proteins and their chromosomal binding sites is revealing new insights into the mechanisms that bring homologs together to ensure proper chromosome segregation.
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