The meiotic chromosome axis organizes chromatin and sets the stage for homolog pairing and recombination. Meiotic HORMA domain proteins (mHORMADs) are conserved axis components that conformationally transform during target binding. In C. elegans, four functionally distinct mHORMADs directly interact, but how binding between them is restricted to axis assembly is unknown. Using a mutation in the mHORMADs that delays axis assembly, we isolated a suppressor mutation in a TRiC (Tailless complex peptide 1 Ring Complex) chaperonin subunit that restored mHORMAD localization. CCT-4 associates with meiotic chromatin and forms in vivo complexes with mHORMADs, while germline disruption of TRiC results in axis defects, indicating a nuclear function for TRiC alongside meiotic chromosomes. We propose that chromosome-associated TRiC locally folds mHORMADs into the binding-competent conformation required for axis morphogenesis. More broadly, our results support the model that spatially-restricted folding by TRiC/CCT is a mechanism of controlling the assembly of multimeric complexes that function in tightly co-ordinated events.

Canada's Michael Smith Genome Sciences Centre at BC Cancer Vancouver BC Canada

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Biology McGill University Montreal QC Canada

Department of Medical Genetics University of British Columbia Vancouver BC Canada

Max Perutz Labs Vienna Biocenter Campus Vienna Austria

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Zickler, D. & Kleckner, N. Meiosis: Dances between homologs. PubMed DOI

Moses, M. J. Structure and function of the synaptonemal complex. PubMed

Zickler, D. & Kleckner, N. Meiotic chromosomes: integrating structure and function. PubMed DOI

Hughes, S. E. & Hawley, R. S. Alternative synaptonemal complex structures: Too much of a good thing?. PubMed DOI

Rog, O. & Dernburg, A. F. Direct visualization reveals kinetics of meiotic chromosome synapsis. PubMed DOI PMC

Pollard, M. G., Rockmill, B., Oke, A., Anderson, C. M. & Fung, J. C. Kinetic analysis of synaptonemal complex dynamics during meiosis of yeast Saccharomyces cerevisiae reveals biphasic growth and abortive disassembly. PubMed DOI PMC

Zickler, D. & Kleckner, N. Recombination, pairing, and synapsis of homologs during meiosis. PubMed PMC

Phillips, C. M. et al. HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis. PubMed DOI PMC

Phillips, C. M. & Dernburg, A. F. A family of zinc-finger proteins is required for chromosome-specific pairing and synapsis during meiosis in C. elegans. PubMed DOI

Zetka, M., Paouneskou, D. & Jantsch, V. The nuclear envelope, a meiotic jack-of-all-trades. PubMed DOI

Couteau, F., Nabeshima, K., Villeneuve, A. & Zetka, M. A component of C. elegans meiotic chromosome axes at the interface of homolog alignment, synapsis, nuclear reorganization, and recombination. PubMed DOI

Couteau, F. & Zetka, M. HTP-1 coordinates synaptonemal complex assembly with homolog alignment during meiosis in C. elegans. PubMed DOI PMC

Martinez-Perez, E. & Villeneuve, A. M. HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during C. elegans meiosis. PubMed DOI PMC

Goodyer, W. et al. HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis. PubMed DOI

Bohr, T., Ashley, G., Eggleston, E., Firestone, K. & Bhalla, N. Synaptonemal complex components are required for meiotic checkpoint function in Caenorhabditis elegans. PubMed DOI PMC

Grey, C. & de Massy, B. Chromosome organization in early meiotic prophase. PubMed DOI PMC

Ur, S. N. & Corbett, K. D. Architecture and dynamics of meiotic chromosomes. PubMed DOI

Prince, J. P. & Martinez-Perez, E. Functions and regulation of meiotic HORMA-domain proteins. PubMed PMC

Sironi, L. et al. Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a ‘safety belt’ binding mechanism for the spindle checkpoint. PubMed DOI PMC

Mapelli, M. et al. Determinants of conformational dimerization of Mad2 and its inhibition by p31comet. PubMed DOI PMC

Luo, X. et al. The Mad2 spindle checkpoint protein has two distinct natively folded states. PubMed DOI

Gu, Y., Desai, A. & Corbett, K. D. Evolutionary dynamics and molecular mechanisms of HORMA domain protein signaling. PubMed DOI

West, A. M. V., Komives, E. A. & Corbett, K. D. Conformational dynamics of the Hop1 HORMA domain reveal a common mechanism with the spindle checkpoint protein Mad2. PubMed DOI PMC

Hollingsworth, N. M. & Byers, B. HOP1: a yeast meiotic pairing gene. PubMed DOI PMC

Schwacha, A. & Kleckner, N. Identification of joint molecules that form frequently between homologs but rarely between sister chromatids during yeast meiosis. PubMed DOI

Shin, Y. H. et al. Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis. PubMed DOI PMC

Daniel, K. et al. Meiotic homologue alignment and its quality surveillance are controlled by mouse HORMAD1. PubMed DOI PMC

Kogo, H. et al. HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity. PubMed DOI

Wojtasz, L. et al. Meiotic DNA double-strand breaks and chromosome asynapsis in mice are monitored by distinct HORMAD2-independent and -dependent mechanisms. PubMed DOI PMC

Sanchez-Moran, E., Santos, J. L., Jones, G. H. & Franklin, F. C. ASY1 mediates AtDMC1-dependent interhomolog recombination during meiosis in Arabidopsis. PubMed DOI PMC

Kim, Y. et al. The chromosome axis controls meiotic events through a hierarchical assembly of HORMA domain proteins. PubMed DOI PMC

Kim, Y., Kostow, N. & Dernburg, A. F. The chromosome axis mediates feedback control of CHK-2 to ensure crossover formation in C. elegans. PubMed DOI PMC

Ferrandiz, N. et al. Spatiotemporal regulation of Aurora B recruitment ensures release of cohesion during C. elegans oocyte meiosis. PubMed DOI PMC

Martinez-Perez, E. et al. Crossovers trigger a remodeling of meiotic chromosome axis composition that is linked to two-step loss of sister chromatid cohesion. PubMed DOI PMC

Severson, A. F., Ling, L., van Zuylen, V. & Meyer, B. J. The axial element protein HTP-3 promotes cohesin loading and meiotic axis assembly in C. elegans to implement the meiotic program of chromosome segregation. PubMed DOI PMC

Milano, C. R. et al. Chromatin binding by HORMAD proteins regulates meiotic recombination initiation. PubMed DOI PMC

Zetka, M. C., Kawasaki, I., Strome, S. & Muller, F. Synapsis and chiasma formation in Caenorhabditis elegans require HIM-3, a meiotic chromosome core component that functions in chromosome segregation. PubMed DOI PMC

Nabeshima, K., Villeneuve, A. M. & Hillers, K. J. Chromosome-wide regulation of meiotic crossover formation in Caenorhabditis elegans requires properly assembled chromosome axes. PubMed DOI PMC

Barroso, C. et al. Two structurally mobile regions control the conformation and function of metamorphic meiotic HORMAD proteins. Preprint at 10.1101/2024.08.05.606648 (2024).

Bhalla, N. PCH-2 and meiotic HORMADs: A module for evolutionary innovation in meiosis?. PubMed DOI PMC

Joshi, N., Barot, A., Jamison, C. & Borner, G. V. Pch2 links chromosome axis remodeling at future crossover sites and crossover distribution during yeast meiosis. PubMed DOI PMC

Miao, C. et al. Central region component1, a novel synaptonemal complex component, is essential for meiotic recombination initiation in rice. PubMed DOI PMC

Lambing, C. et al. Arabidopsis PCH2 Mediates Meiotic Chromosome Remodeling and Maturation of Crossovers. PubMed DOI PMC

Chotiner, J. Y. et al. TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis. PubMed PMC

Deshong, A. J., Ye, A. L., Lamelza, P. & Bhalla, N. A quality control mechanism coordinates meiotic prophase events to promote crossover assurance. PubMed DOI PMC

Lopez, T., Dalton, K. & Frydman, J. The mechanism and function of group II chaperonins. PubMed DOI PMC

Yam, A. Y. et al. Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies. PubMed DOI PMC

Russmann, F. et al. Folding of large multidomain proteins by partial encapsulation in the chaperonin TRiC/CCT. PubMed DOI PMC

Joly, E. C., Tremblay, E., Tanguay, R. M., Wu, Y. & Bibor-Hardy, V. TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix. PubMed DOI

Gerner, C. et al. Reassembling proteins and chaperones in human nuclear matrix protein fractions. PubMed DOI

Kasembeli, M. et al. Modulation of STAT3 folding and function by TRiC/CCT chaperonin. PubMed DOI PMC

Saegusa, K. et al. Caenorhabditis elegans chaperonin CCT/TRiC is required for actin and tubulin biogenesis and microvillus formation in intestinal epithelial cells. PubMed DOI PMC

Soues, S., Kann, M. L., Fouquet, J. P. & Melki, R. The cytosolic chaperonin CCT associates to cytoplasmic microtubular structures during mammalian spermiogenesis and to heterochromatin in germline and somatic cells. PubMed DOI

Gvozdenov, Z., Kolhe, J. & Freeman, B. C. The nuclear and DNA-associated molecular chaperone network. PubMed PMC

Dekker, C. et al. The interaction network of the chaperonin CCT. PubMed DOI PMC

Gvozdenov, Z. et al. TRiC/CCT chaperonin governs RNA polymerase II activity in the nucleus to support RNA homeostasis. Preprint at 10.1101/2024.09.26.615188 (2024).

Ahuja, J. S. et al. Control of meiotic pairing and recombination by chromosomally tethered 26S proteasome. PubMed DOI PMC

Frokjaer-Jensen, C. et al. Single-copy insertion of transgenes in Caenorhabditis elegans. PubMed DOI PMC

Cong, Y. et al. 4.0-A resolution cryo-EM structure of the mammalian chaperonin TRiC/CCT reveals its unique subunit arrangement. PubMed DOI PMC

Dernburg, A. F. et al. Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis. PubMed DOI

MacQueen, A. J., Colaiacovo, M. P., McDonald, K. & Villeneuve, A. M. Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans. PubMed DOI PMC

Harper, N. C. et al. Pairing centers recruit a Polo-like kinase to orchestrate meiotic chromosome dynamics in C. elegans. PubMed DOI PMC

Labella, S., Woglar, A., Jantsch, V. & Zetka, M. Polo kinases establish links between meiotic chromosomes and cytoskeletal forces essential for homolog pairing. PubMed DOI

MacQueen, A. J. & Villeneuve, A. M. Nuclear reorganization and homologous chromosome pairing during meiotic prophase require C. elegans chk-2. PubMed DOI PMC

Blazickova, J. itka et al. Overlapping and separable activities of BRA-2 and HIM-17 promote occurrence and regulation of pairing and synapsis during Caenorhabditis elegans meiosis. PubMed DOI PMC

Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. PubMed DOI PMC

Elaswad, M. T. et al. The CCT chaperonin and actin modulate the ER and RNA-binding protein condensation during oogenesis and maintain translational repression of maternal mRNA and oocyte quality. PubMed DOI PMC

Ma, X. et al. CCT2 is an aggrephagy receptor for clearance of solid protein aggregates. PubMed DOI

Leroux, M. R., Ma, B. J., Batelier, G., Melki, R. & Candido, E. P. Unique structural features of a novel class of small heat shock proteins. PubMed DOI

Noormohammadi, A. et al. Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan. PubMed DOI PMC

Silva, N. et al. The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression. PubMed DOI

Gestaut, D. et al. Structural visualization of the tubulin folding pathway directed by human chaperonin TRiC/CCT. PubMed DOI PMC

Rog, O., Kohler, S. & Dernburg, A. F. The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors. PubMed PMC

Banks, C. A. S. et al. Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly. PubMed DOI PMC

Dekker, C. On the role of the chaperonin CCT in the just-in-time assembly process of APC/CCdc20. PubMed DOI

Rao, H. B. et al. A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination. PubMed DOI PMC

Brenner, S. The genetics of Caenorhabditis elegans. PubMed DOI PMC

Woglar, A. et al. SUN-1 phosphorylation is part of a surveillance mechanism to coordinate chromosome synapsis and recombination with meiotic progression and chromosome movement. PubMed DOI PMC

Tunyasuvunakool, K. et al. Highly accurate protein structure prediction for the human proteome. PubMed DOI PMC

Paix, A., Folkmann, A. & Seydoux, G. Precision genome editing using CRISPR-Cas9 and linear repair templates in C. elegans. PubMed DOI PMC

Janisiw, E., Dello Stritto, M. R., Jantsch, V. & Silva, N. BRCA1-BARD1 associate with the synaptonemal complex and pro-crossover factors and influence RAD-51 dynamics during Caenorhabditis elegans meiosis. PubMed DOI PMC