Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved closure motif region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to other previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation. Author summary To segregate properly in meiosis, cohesion between replicated chromosomes must remain after the first meiotic cell division, so chromosomes can be held together until they finally separate in the second division. While the majority of organisms use centromeres to protect chromosome cohesion in the first division, the nematode worm C. elegans, which lacks single centromeres, instead protects cohesion only on a segment of the chromosome known as the long arm. The long arm (and its complement, the short arm) are known to accumulate specific proteins and protein modifications, but it is not known how the short and long arms are first distinguished, nor how their separate functions are carried out. We report here that the chromosome axis protein HIM-3 and its modification by phosphorylation is important for ensuring the robust establishment of short and long arm functions. We show that phosphorylated HIM-3 partitions to the short arms after crossover recombination sites are designated, and HIM-3 mutants that mimic constitutive phosphorylation delay the normal establishment of the two complementary arm domains. Our findings reveal another layer of regulation to an outstanding mystery in chromosome biology.