Biology subjects

Dunce, J. M.

Publications and source records attributed to Dunce, J. M..

3 recordsLinked to original sources

bioRxiv2022

Parallel recruitment pathways contribute to synaptonemal complex assembly during mammalian meiosis

During meiosis, the synaptonemal complex (SC) assembles between paired chromosomes, binding them together in close apposition, and facilitating recombination. SC assembly is thought to occur through the hierarchical zipper-like recruitment of axial elements, followed by transverse filaments and then central elements. However, the rapidity of SC formation in mammals has hitherto hindered investigation of its assembly mechanisms and their relationship with recombination. Using super-resolution imaging of separation-of-function mouse mutants, we show that, contrary to the hierarchical assembly model, central element protein SYCE2 is recruited to recombination sites early in SC assembly, and independently of SYCP1-containing transverse filaments. Further, SYCE2-TEX12 binds DNA in vitro, and SYCE2-containing bridges physically link paired chromosomes at recombination sites prior to transverse filament recruitment and chromosome synapsis. These data suggest that mammals integrate parallel recruitment pathways to assemble a mature SC: one recruiting central element proteins to recombination sites, and another recruiting transverse filaments to chromosomes.

cell biology↗

bioRxiv2022

Structural maturation of SYCP1-mediated meiotic chromosome synapsis through conformational remodelling by molecular adapter SYCE3

In meiosis, a supramolecular protein structure, the synaptonemal complex (SC), assembles between homologous chromosomes to facilitate their recombination. Mammalian SC formation is thought to involve hierarchical zipper-like assembly of an SYCP1 protein lattice that recruits stabilising central element (CE) proteins as it extends. Here, we combine biochemical approaches with separation-of-function mutagenesis in mice to uncover that, rather than stabilising the SYCP1 lattice, the CE protein SYCE3 actively remodels this structure during synapsis. We find that SYCP1 tetramers undergo conformational change into 2:1 heterotrimers upon SYCE3-binding, removing their assembly interfaces and disrupting the SYCP1 lattice. SYCE3 then establishes a new lattice by its self-assembly mimicking the role of the disrupted interface in tethering together SYCP1 dimers. SYCE3 also interacts with CE complexes SYCE1-SIX6OS1 and SYCE2-TEX12, providing a mechanism for their recruitment. Thus, SYCE3 remodels the SYCP1 lattice into a CE-binding integrated SYCP1-SYCE3 lattice to achieve long-range synapsis by a mature SC.

biochemistry↗

bioRxiv2020

Structural basis of meiotic chromosome synaptic elongation through hierarchical fibrous assembly of SYCE2-TEX12

The synaptonemal complex (SC) is a supramolecular protein assembly that mediates synapsis between homologous chromosomes during meiosis. SC elongation along the chromosome length (up to 24 m) depends on its midline -fibrous component SYCE2-TEX12. Here, we report X-ray crystal structures of SYCE2-TEX12 as an individual building-block and upon assembly within a fibrous lattice. We combine these structures with mutagenesis, biophysics and electron microscopy to reveal the hierarchical mechanism of SYCE2-TEX12 fibre assembly. SYCE2-TEX12s building-blocks are 2:2 coiled-coils which dimerise into 4:4 hetero-oligomers and interact end-to-end and laterally to form 10-nm fibres, which intertwine within 40-nm bundled micrometre-long fibres that define the SCs midline structure. This assembly mechanism bears striking resemblance with intermediate filament proteins vimentin, lamin and keratin. Thus, SYCE2-TEX12 exhibits behaviour typical of cytoskeletal proteins to provide an -fibrous SC backbone that structurally underpins synaptic elongation along meiotic chromosomes.

biochemistry↗