Biology subjects

Zetka, M.

Publications and source records attributed to Zetka, M..

5 recordsLinked to original sources

bioRxiv2026

CYB-4/CDK-1 coordinates timing of meiotic entry, chromosome morphogenesis and oocyte maturation in C. elegans

Meiotic chromosome segregation requires the earlier coordination of chromosome morphogenesis with cell-cycle progression. In C. elegans, the remodeling of chromosomes in preparation for the meiotic divisions and oocyte maturation is regulated by the master cell-cycle regulator cyclin-dependent kinase 1 (CDK-1). Here, we identify CYB-4 as a meiosis-specific B-type cyclin that is required for CDK-1-dependent functions in meiotic prophase. In a genetic suppressor analysis of a mutant defective in chromosome axis assembly, we isolated a null allele that revealed a function for CYB-4 in regulating chromosome structure at two key prophase transitions. Loss of CYB-4 first delays meiotic entry and the onset of chromosome axis formation, and at pachytene exit delays chromatin condensation, bivalent remodeling, and oocyte maturation. The defects in timely CO formation and bivalent packaging that accompany these delays are ultimately resolved before prophase exit, indicating that CYB-4 is required for the scheduling of events rather than if they occur. Together, our findings provide evidence that CDK-1 activity during meiotic prophase is defined by CYB-4 and support a model in which CYB-4/CDK-1 are essential for the sharp transitions at prophase entry and pachytene exit that coordinate chromosome morphogenesis with meiotic progression.

cell biology↗

bioRxiv2026

ZHP-2/HEI10 generates CO precursors and triggers procrossover factor coarsening and CO formation through Polo kinase recruitment

During meiosis, programmed DNA double-strand breaks (DSBs) are repaired with the homolog to form crossovers (COs) essential for chromosome segregation, or noncrossovers (nCOs) to restore genomic integrity. Only a few recombination intermediates will become COs and these sites are progressively enriched in proCO factors at the expense of nCO sites, referred to as coarsening. Here, we show that in C. elegans this process is engineered by ZHP-2/HEI10, a conserved E3 ligase that has functions at early and late stages of CO formation. Early on, ZHP-2-mediated loss of RMH-1/RMI1 and HIM-6/BLM from strand exchange intermediates is required for joint molecule formation and nCO repair. In zhp-2 mutants, proCO factors accumulate at HR sites, leading to defects in CO formation and CO spacing. We find that Polo kinase recruitment to a ZHP-2 at CO precursors signals an end to further DSB formation, and triggers proCO factor coarsening and CO formation. We propose that ZHP-2 disassembles proCO factors from recombination intermediates until it is inactivated at CO precursors through Polo kinase recruitment, leading to stabilization of proCO factors, and resolution of joint molecules as crossovers. Our study reveals that ZHP-2/HEI10 is the central component of a Polo kinase-driven switch that initiates proCO factor coarsening and execution of crossing over.

cell biology↗

bioRxiv2025

A nuclear TRiC/CCT chaperonin assembles meiotic HORMAD proteins into chromosome axes competent for crossing over

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/CCT 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-tethered TRiC folds mHORMADs into a conformationally active local population 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.

cell biology↗

bioRxiv2024

Distinct intersecting pathways link homolog pairing to initiation of meiotic chromosome synapsis

Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and Synaptonemal Complex assembly (SC) at their interface. Here, we investigate on new factors that promote and coordinate these events during C. elegans meiosis. We identify BRA-2 (BMP Receptor Associated family member 2) as an interactor of HIM-17, previously shown to promote double-strand break formation. We found that loss of bra-2 specifically impairs synapsis licensing without affecting homologs recognition, SC maintenance or chromosome movement. Double mutant analysis revealed a previously unrecognized role for HIM-17 in promoting homolog pairing under dysfunctional SC assembly, without perturbing nuclear envelope recruitment of factors required for chromosome movement. We provide evidence that bra-2 and him-17 act in distinct pathways, exerting partially redundant functions in SC licensing, as well as separable roles in regulating homologs pairing. Altogether, our findings unveil novel mechanisms that ensure stabilization of homologous chromosome interaction via SC licensing upon homology assessment.

cell biology↗

bioRxiv2019

NHJ-1 regulates canonical non-homologous end joining in Caenorhabditis elegans

Canonical non-homologous end joining (cNHEJ) is a near-universally conserved pathway for the repair of DNA double-strand breaks (DSBs). While the cNHEJ pathway encompasses more than a dozen factors in vertebrates and is similarly complex in other eukaryotes, in the nematode C. elegans the entire known cNHEJ toolkit consists of two proteins that comprise the Ku ring complex, cku-70 and cku-80, and the terminal ligase lig-4. Here, we report the discovery of nhj-1 as the fourth cNHEJ factor in C. elegans. Observing a difference in the phenotypic response to ionizing radiation (IR) between two lines of the wild type N2 strain, we mapped the locus causative of IR-sensitivity to a candidate on chromosome V. Using CRISPR-Cas9 mutagenesis, we show that disrupting the nhj-1 sequence induces IR-sensitivity in an IR-resistant background. Double mutants of nhj-1 and the cNHEJ factors lig-4 or cku-80 do not exhibit additive IR-sensitivity, arguing that nhj-1 is a member of the cNHEJ pathway. Furthermore, like the loss of lig-4, the loss of nhj-1 in the com-1 genetic background, in which meiotic DSBs are repaired by cNHEJ instead of homologous recombination, increased the number of DAPI-staining bodies in diakinesis, consistent with increased chromosome fragmentation in the absence of cNHEJ repair. Finally, we show that NHJ-1 localizes to many somatic nuclei in the L1 larva, but not the primordial germline, which is in accord with a role in the predominantly somatically active cNHEJ. Although nhj-1 shares no sequence homology with other known eukaryotic cNHEJ factors and is taxonomically restricted to the Rhadbitid family, its discovery underscores the evolutionary plasticity of even highly conserved pathways, and may represent a springboard for further characterization of cNHEJ in C. elegans.

genetics↗