Control of meiotic pairing and recombination by chromosomally tethered 26S proteasome

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Science  27 Jan 2017:
Vol. 355, Issue 6323, pp. 408-411
DOI: 10.1126/science.aaf4778

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Proteasomes and SUMO wrestle chromosomes

Meiosis is the double cell division that generates haploid gametes from diploid parental cells. Pairing of homologous chromosomes during the first meiotic division ensures that each gamete receives a complete set of chromosomes. The proteasome, on the other hand, is a molecular machine that degrades proteins tagged for destruction within the cell (see the Perspective by Zetka). Ahuja et al. show that the proteasome is also involved in ensuring that homologous chromosomes pair with each other during meiosis. Rao et al. show that the SUMO (small ubiquitin-like modifier) protein, ubiquitin, and the proteasome localize to the axes between homologous chromosomes. In this location, they help mediate chromosome pairing and recombination between homologs.

Science, this issue p. 349, p. 408; see also p. 403


During meiosis, paired homologous chromosomes (homologs) become linked via the synaptonemal complex (SC) and crossovers. Crossovers mediate homolog segregation and arise from self-inflicted double-strand breaks (DSBs). Here, we identified a role for the proteasome, the multisubunit protease that degrades proteins in the nucleus and cytoplasm, in homolog juxtaposition and crossing over. Without proteasome function, homologs failed to pair and instead remained associated with nonhomologous chromosomes. Although dispensable for noncrossover formation, a functional proteasome was required for a coordinated transition that entails SC assembly between longitudinally organized chromosome axes and stable strand exchange of crossover-designated DSBs. Notably, proteolytic core and regulatory proteasome particles were recruited to chromosomes by Zip3, the ortholog of mammalian E3 ligase RNF212, and SC protein Zip1 . We conclude that proteasome functions along meiotic chromosomes are evolutionarily conserved.

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