The fundamental function of meiosis, segregation of the maternal and paternal chromosomes, is facilitated by reciprocal recombination and intimate juxtaposition (synapsis) between the homologous chromosomes in meiotic prophase. Homolog synapsis, mediated by the synaptonemal complex (SC), is preceded by a stage of pairing between the centromeres of nonhomologous chromosomes. This pairing, named nonhomologous centromere coupling (NCC), depends upon the meiotic cohesin Rec8 and the SC protein Zip1. Nonhomologously coupled centromeres (NCCs), if remain tethered, must interfere with complete homolog synapsis (SC formation). Recent experiments demonstrate the existence of a mechanism that regulates NCC. Importantly, this is part of a regulatory network which couples dissolution of the NCCs with SC formation between the homologous chromosomes, thereby ensuring appropriate meiotic chromosome interactions. This paper reviews this network and presents speculations relating to the initiation of SC formation at centromere. 1. Introduction Cell biologists working on meiosis, the cell division that segregates the maternal and paternal chromosomes to produce haploid gametes from diploid parent cells, have ever been fascinated by the ballet between chromosomes that occupy a substantial part of the meiotic prophase (reviewed in [1, 2]). This culminates into initial side-by-side alignment (named pairing) of the two homologous chromosomes, which subsequently converts to intimate physical juxtaposition (named synapsis) of the two homologs along their entire length. Synapsis between the homologous chromosomes is mediated by a complex proteinaceous structure named synaptonemal complex (SC). (SC may also form between nonhomologous chromosomes or segments of chromosomes that are not homologous.) The SC is a tripartite organelle in which a central element (CE) connects two lateral elements (LEs); each LE represents the merged axes formed along the length of the two sister chromatids (reviewed in [3]). In many organisms, homolog synapsis and SC formation are stringently coupled with the programmed induction of meiotic DNA double strand-breaks (DSBs) by the conserved topoisomerase Spo11, which initiates the process of reciprocal interhomolog recombination (reviewed in [4]). A twist in the tale came from the Roeder laboratory [5]. It was demonstrated that, in budding yeast strain lacking Spo11, a stage of pairing, named Nonhomologous Centromere Coupling (NCC), between the centromeres of nonhomologous chromosomes precedes the homology-dependent synapsis. (The nonhomologously
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