Accurate segregation of chromosomes during meiosis requires that they pair, synapse, and undergo crossover recombination with their homologs. Although genetic studies over the last few decades have identified a list of components that are essential for these processes, it remains largely unknown how protein machines work together to orchestrate chromosome dynamics.
We are addressing these long-standing questions by combining biochemical and structural analysis using purified components, with the ability to examine meiosis in the context of highly tractable C. elegans germline.
Structure and function of the synaptonemal complex
The synaptonemal complex (SC) is a zipper-like protein assembly that links homologous chromosomes to regulate recombination and segregation during meiosis. Despite the conserved appearance of the SC across species, little is known about how individual components interact with each other to assemble into high-ordered structures.
Our lab has identified previously missing SC subunits in C. elegans (Hurlock et al., 2020; Blundon et al., 2024), which enabled us to reconstitute a soluble protein complex consisting of six SC components with a defined stoichiometry using purified components (Blundon et al., 2024). We hypothesize that this SYP/SKR complex represents the fundamental unit for SC assembly. This breakthrough has uniquely positioned us to address the long-standing questions regarding the molecular architecture and assembly mechanisms of the SC.
(A) Chromosome dynamics during meiosis. (B) A schematic showing the structure of the synaptonemal complex (SC). The complete list of SC subunits in C. elegans is shown below. (C) In vitro reconstitution of a soluble complex comprising the six core subunits of the SC central region using a bacterial polycistronic expression system (Blundon et al., 2024).
We are currently characterizing the stoichiometry and molecular organization of the SYP/SKR complex using mass photometry, crosslinking mass spectrometry, and structural biology. We will also determine the requirements that underlie SC assembly by combining genetics and in vitro assays.
Signaling Cascades in meiotic chromosome dynamics
Key aspects of chromosome dynamics in meiosis, as in mitosis, are controlled by phosphorylation-dependent regulation. A central regulator of SC assembly in C. elegans is the Polo-like kinase (PLK) family. Meiosis-specific PLK-2 localizes to specialized chromosome regions known as pairing centers and drives homolog pairing and synapsis. PLK-2 is later recruited to the crossover-designated site and the SC to control chromosome remodeling required for homolog separation during meiosis. However, the identity of PLK substrates essential for these processes remains unknown.
Model for targeting PLK-2 to distinct subnuclear structures during meiotic prophase in C. elegans (Brandt et al., 2020)
We continue to delineate the signaling cascades by major cell cycle kinases and establish the conserved regulatory mechanisms that orchestrate meiotic chromosome dynamics. Our work will ultimately shed light into how organisms faithfully transmit genetic information from one generation to the next.
