Faithful transmission of the genome through sexual reproduction requires precise reduction of genome copy number during gametogenesis to produce haploid sperm and eggs. Meiosis therefore entails unique steps, that are absent from mitosis, to tether homologous chromosomes together during prophase of meiosis I and to separate homologs and then sister chromatids during anaphase of meiosis I and II. We show that HTP-3, a known component of the axial element (AE) that assembles along meiotic chromosomes and promotes crossover recombination, molecularly links these meiotic innovations. When meiosis begins, sister chromatids are held together by sister chromatid cohesion (SCC), mediated by a protein complex called cohesin. Homologs become linked during crossover recombination. Once recombination is complete, SCC around the crossover holds homologs and sisters together. Their successive separation requires the stepwise proteolysis of Rec8, a meiosis-specific cohesin subunit. During meiosis I, cohesin regulators protect Rec8 locally, at discrete domains of each homolog pair, to keep sisters together. We have found that global regulation of cohesin loading by HTP-3 is also required to forestall sister separation in anaphase I, and that cohesin, in turn, is required for HTP-3 loading and AE assembly. Unexpectedly, REC-8, the known REC-8 paralog COH-3 and the previously unknown paralog COH-4 are together essential for AE assembly. In contrast, REC-8 alone can keep sisters together after anaphase I; consequently, sister chromatids segregate away from one another in meiosis I of rec-8
mutants (premature equational division). In a genetic screen for additional factors required to maintain SCC until meiosis II, we identified HTP-3, already known to promote meiotic double strand DNA break formation, homolog pairing, synapsis and recombination. We show that HTP-3 recruits all known AE components to meiotic chromosomes. Additionally, HTP-3 promotes loading of REC-8 containing cohesin complexes, the first demonstrated requirement for an AE protein in cohesin axis assembly. In htp-3
mutants, sister chromatids separate equationally in anaphase I. Thus, HTP-3 is required for multiple events that distinguish meiosis from mitosis. Moreover, our data suggest that interdependent loading of HTP-3 and cohesin is a principal step in assembly of the meiotic chromosomal axis.