Spatial Regulation of Polo-Like Kinase Activity During Caenorhabditis elegans Meiosis by the Nucleoplasmic HAL-2/HAL-3 Complex

• Published in: Genetics (Austin) 2019-09, Vol.213 (1), p.79-96
• Main Authors: Roelens, Baptiste, Barroso, Consuelo, Montoya, Alex, Cutillas, Pedro, Zhang, Weibin, Woglar, Alexander, Girard, Chloe, Martinez-Perez, Enrique, Villeneuve, Anne M
• Format: Article
• Language: English
• Subjects: Alignment; Animals; Assembly; Axes (reference lines); Bioinformatics; Caenorhabditis elegans; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell cycle; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cellular structure; Chromosomes; Crossovers; Defects; Deoxyribonucleic acid; DNA; Gene expression; Genetics; Germ cells; Homology; Investigations; Kinases; Localization; Meiosis; Mutants; Mutation; Nematodes; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphorylation; Polo-like kinase; Prophase; Protein Binding; Protein Serine-Threonine Kinases - metabolism; Proteins; Synaptonemal complex; Synaptonemal Complex - genetics; Synaptonemal Complex - metabolism
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.119.302479

Proper partitioning of homologous chromosomes during meiosis relies on the coordinated execution of multiple interconnected events: Homologs must locate, recognize, and align with their correct pairing partners. Further, homolog pairing must be coupled to assembly of the synaptonemal complex (SC), a meiosis-specific tripartite structure that maintains stable associations between the axes of aligned homologs and regulates formation of crossovers between their DNA molecules to create linkages that enable their segregation. Here, we identify HAL-3 (Homolog Alignment 3) as an important player in coordinating these key events during meiosis. HAL-3, and the previously identified HAL-2, are interacting and interdependent components of a protein complex that localizes to the nucleoplasm of germ cells. (or ) mutants exhibit multiple meiotic prophase defects including failure to establish homolog pairing, inappropriate loading of SC subunits onto unpaired chromosome axes, and premature loss of synapsis checkpoint protein PCH-2. Further, loss of function results in misregulation of the subcellular localization and activity of Polo-like kinases (PLK-1 and PLK-2), which dynamically localize to different defined subnuclear sites during wild-type prophase progression to regulate distinct cellular events. Moreover, loss of PLK-2 activity partially restores tripartite SC structure in a mutant background, suggesting that the defect in pairwise SC assembly in mutants reflects inappropriate PLK activity. Together, our data support a model in which the nucleoplasmic HAL-2/HAL-3 protein complex constrains both localization and activity of meiotic Polo-like kinases, thereby preventing premature interaction with stage-inappropriate targets.