Presentation/Session Information

Session Information

Session Title: Cell Division and Cell Death Session Type: Parallel
Session Location: Northwest Auditorium Session Time: Thu, Jun 25 8:30AM - 11:30AM

Presentation Information

Program Number: 55 Presentation Time: 10:18AM - 10:30AM

Presentation Content

Dynamic phosphoregulation of axis proteins underlies chromosome remodeling during meiosis.Yumi Kim 1,2, Scott C. Rosenberg 3,4, Nora Kostow 1,2, Ofer Rog 1,2, Kevin D. Corbett 3,4, Abby F. Dernburg 1,2. 1)Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA; 2)Howard Hughes Medical Institute; 3)Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA; 4)Ludwig Institute for Cancer Research

Segregation of chromosomes in meiosis requires their dramatic, stepwise reorganization during meiotic prophase. Each chromosome must pair, synapse, and recombine with its homolog to achieve the stable bivalent structures that biorient and then divide during Meiosis I. A fundamental mystery is how these events are coordinated during the meiotic cell cycle. Pairing, synapsis, and recombination depend on the formation of linear “axes” along each chromosome at meiotic entry, followed by assembly of the synaptomemal complex (SC) between paired axes. Chromosome axes in C. elegans are comprised of cohesins and four related HORMA domain proteins: HIM-3, HTP-1, HTP-2, and HTP-3. We recently reported that the largest of these proteins, HTP-3, recruits the other three paralogs through short peptide sequences (closure motifs) in its C-terminal tail, which are bound by the HORMA domains of HTP-1, HTP-2, and HIM-3 (Kim, Rosenberg, et al., 2014). Here we show that these interactions are dynamically regulated by phosphorylation of the closure motifs in HTP-3 by two meiotic kinases, CHK-2 and PLK-2. Phosphorylation of the four central motifs reduces their binding affinity for HIM-3, and occurs in two temporally distinct waves. In early meiosis, phosphorylation along the entire axis by CHK-2 is required for efficient synapsis. A second wave of phosophorylation by PLK-2 occurs after crossover formation, and specifies the “short arm” of the bivalent where cohesion will be released during the first meiotic division. This second wave of HTP-3 phosphorylation requires both crossover formation and recruitment of PLK-2 to the chromosomes through a binding site in a SC component, SYP-1. Thus, phosphorylation-dependent regulation of HORMA domain protein assembly promotes dynamic remodeling of chromosome axes during meiotic progression, and is essential for proper segregation of holocentric chromosomes in C. elegans meiosis.




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