The functional organisation of the centromere and kinetochore during meiosis

Current Opinion in Cell Biology, Journal Year: 2025, Volume and Issue: 94, P. 102486 - 102486

Published: Feb. 26, 2025

Language: Английский

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

Published: March 3, 2025

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

Language: Английский

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Overlapping and separable activities of BRA-2 and HIM-17 promote occurrence and regulation of pairing and synapsis during Caenorhabditis elegans meiosis

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 13, 2025

Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and their synaptonemal complex (SC) mediated stabilization. Here, we investigate factors that promote coordinate these events during C. elegans meiosis. We identify BRA-2 (BMP Receptor Associated family member 2) as an interactor HIM-17, previously shown to double-strand break formation. found loss bra-2 impairs synapsis elongation without affecting homolog recognition, chromosome movement or SC maintenance. Epistasis analyses reveal unrecognized activities for HIM-17 in regulating pairing assembly a partially overlapping manner with BRA-2. show removing him-17 restores nuclear clustering, recruitment PLK-2 at periphery, abrogation ectopic htp-1 mutants, suggesting intact CHK-2-mediated signaling presence barrier prevents polymerization absence homology. Our findings shed light on regulatory mechanisms ensuring faithful synapsis. Chromosome must be tightly regulated Blazickova et al. BRA-2, together exert both separable functions promoting establishment between chromosomes.

Language: Английский

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CTCF-anchored chromatin loop dynamics during human meiosis

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 20, 2025

Abstract Background During meiosis, the mammalian genome is organised within chromatin loops, which facilitate synapsis, crossing over and chromosome segregation, setting stage for recombination events generation of genetic diversity. Chromatin looping thought to play a major role in establishment cross overs during prophase I diploid early primary spermatocytes. However, conformation dynamics human meiosis are difficult study experimentally, due transience each cell division difficulty obtaining stage-resolved populations. Here, we employed machine learning framework trained on single ATAC-seq RNA-seq data predict CTCF-anchored spermatogenesis, including types at different stages meiosis. Results We find dramatic changes genome-wide patterns throughout meiosis: compared pre-and-post meiotic germline types, loops spermatocytes more abundant, variable between individual cells, evenly spread genome. In preparation first division, also include longer stretches DNA, encompassing than half total These loop structures then influence rate initiation resolution as overs. contrast, later mature sperm stages, evidence compaction, with being confined telomeric ends chromosomes. Conclusion Overall, that do not orchestrate gene expression seen but important roles recombination, influencing positions DNA breakage events.

Language: Английский

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Cell cycle and age-related modulations of mouse chromosome stiffness

eLife, Journal Year: 2025, Volume and Issue: 13

Published: April 14, 2025

Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness chromosomes offers valuable insight into their structural properties. In this study, we analyzed from metaphase I (MI) II (MII) oocytes. Our results revealed a tenfold increase in (Young’s modulus) MI compared to somatic chromosomes. Furthermore, MII was found be lower than that We examined role meiosis-specific cohesin complexes regulating stiffness. Surprisingly, three mutants did significantly differ wild-type chromosomes, indicating these cohesins may primary determinants Additionally, our findings an age-related for Since aging associated with elevated levels DNA damage, investigated impact etoposide-induced damage on it led reduction Overall, study underscores dynamic cyclical nature stiffness, modulated by both cell cycle factors.

Language: Английский

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