English (United States)
Homologous chromosomes must associate stably in meiosis I in order to segregate correctly amongst the four haploid products. The synaptonemal complex (SC) is the tripartite proteanous structure that stabilizes these interactions. A major component of the SC that spans the distance between aligned homologs is Zip1, which has well- characterized SC assembly and crossover recombination functions. While many previous studies believed these functions to be linked, more recent studies have shown that certain Zip1 mutations can display distinct separate phenotypes for the two alleles. Our study focuses on a deletion of the sequence corresponding to residues S2- S9 in the S. cerevisiae Zip1 N-terminus region, or the D1 deletion. We observed an elevated level of SUMOylation of Ecm11, suggesting that SC assembly occurs in the zip1-D1 allele, but we also noted a diminishment of Msh4-mediated crossovers in zip1-D1, indicating that the recombination function of Zip1-D1 is significantly impaired. Surprisingly, zip1-D1 displays a slight recovery of crossovers when the E3 SUMO ligase protein, Zip3, is removed. This work also revealed the unexpected finding that zip3 null mutants do not share the same diminishment in crossover recombination as mutants missing the MutS? protein, Msh4, although Zip3 has been presumed to be an essential component in the Msh4 pathway for generating crossovers. We propose that the D1 region may act as a critical regulator of Zip1’s self-assembly behavior that is important for ensuring that SC assembly and crossover recombination are properly coordinated. The residues of Zip1’s D1 region contain charged, repelling forces which may prevent Zip1 self-interactions from occurring at iv the wrong place and/or the wrong time; such Zip1 self-assembly may be detrimental to the maturation of crossover-designated recombination intermediates. In this model, Zip3 also acts to prevent Zip1 self-assembly, perhaps through a direct interaction with Zip1. Finally, this work has contributed insight into a recently revealed role of certain SC proteins in counteracting DNA mismatches.
Parziale, Melanie Patricia, "The D1 Mini Deletion: What a Loss of 8 Amino Acids Reveals About Zip1 Structure and Function" (2016). Honors Theses - All. 1576.
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