Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis.

During sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes, bringing them together and regulating exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper in C. elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose a model whereby the SC brings homologous chromosomes together through two activities: obligate zipping that prevents assembly on unpaired chromosomes; and a tendency to extend pairing interactions along the entire length of the chromosomes. Author summary: Meiosis is a specialized cell division cycle during which maternal and paternal chromosomes are brought together, exchange information and separate into new cells that become gametes, such as sperm, egg or pollen. The Synaptonemal Complex (SC) is a zipper-like structure that assembles between the paternal and maternal chromosomes during meiosis, brings them together and regulates interactions between them. However, our understanding of structure/function relationships within the SC remains limited. Here we focused on one protein in the SC in nematodes—SYP-1—and isolated many random mutations in one of its domains. Two of these mutations had distinct effects on the way chromosomes were brought together and exchanged information. By characterizing these effects we came up with a model that links molecular-scale events in the middle of the SC zipper to chromosome-wide regulation of pairing and genetic exchanges. Future work defining the ultrastructure of the SC in the mutants will allow us to test the predictions of our model and define the mechanism by which the SC carries out its functions. [ABSTRACT FROM AUTHOR]

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