Chromosome separation during Drosophila male meiosis I requires separase-mediated cleavage of the homolog conjunction protein UNO

Author summary For production of sperm and oocytes, precursor cells have to complete meiosis, which comprises two successive divisions. These divisions convert diploid cells into haploid cells. Diploid cells are characterized by the presence of both a maternal and a paternal copy of each chromosome. In contrast, haploid cells have only one copy of each chromosome. Chromosome copy reduction during meiosis requires the pairing of the maternal and paternal copy of each chromosome into a bivalent chromosome in the diploid precursor cell. Bivalents are integrated into the spindle in a bi-polar fashion, with the two chromosomes connected to opposite spindle poles. Once all bivalents are properly bi-oriented, the linkage between the two chromosome copies is destroyed so that they can be pulled apart towards opposite poles. While all sexually reproducing species have to accomplish meiosis, the mechanism for linkage of the two chromosome copies into a bivalent is not invariant. A special type of linkage is used in males of the flyDrosophila melanogasterfor example. Here we describe UNO, a novel protein required for this chromosome linkage. When the linkage needs to be destroyed for chromosome separation during the first meiotic division, UNO is cleaved by a protease known as separase. Regular chromosome segregation during the first meiotic division requires prior pairing of homologous chromosomes into bivalents. During canonical meiosis, linkage between homologous chromosomes is maintained until late metaphase I by chiasmata resulting from meiotic recombination in combination with distal sister chromatid cohesion. Separase-mediated elimination of cohesin from chromosome arms at the end of metaphase I permits terminalization of chiasmata and homolog segregation to opposite spindle poles during anaphase I. Interestingly, separase is also required for bivalent splitting during meiosis I inDrosophilamales, where homologs are conjoined by an alternative mechanism independent of meiotic recombination and cohesin. Here we report the identification of a novel alternative homolog conjunction protein encoded by the previously uncharacterized geneunivalents only(uno). The univalents that are present inunonull mutants at the start of meiosis I, instead of normal bivalents, are segregated randomly. In wild type, UNO protein is detected in dots associated with bivalent chromosomes and most abundantly at the localized pairing site of the sex chromosomes. UNO is cleaved by separase. Expression of a mutant UNO version with a non-functional separase cleavage site restores homolog conjunction in a uno null background. However, separation of bivalents during meiosis I is completely abrogated by this non-cleavable UNO version. Therefore, we propose that homolog separation duringDrosophilamale meiosis I is triggered by separase-mediated cleavage of UNO.