Replication protein-A, RPA, plays a pivotal role in the maintenance of recombination checkpoint in yeast meiosis DOI Creative Commons
Akira Shinohara,

Arivarasan Sampathkumar,

Masaru Ito

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 12, 2023

Abstract DNA double-strand breaks (DSBs) activate damage responses (DDR) in both mitotic and meiotic cells. Meiotic DSBs induce homologous recombination monitored by a DDR called the checkpoint for pachytene exit prophase I. In this study, we showed essential role of single-stranded (ssDNA) binding protein, Replication protein-A (RPA), maintenance during S. cerevisiae meiosis. The depletion an RPA subunit, Rfa1, recombination-defective dmc1 mutant, fully alleviates arrest with persistent unrepaired DSBs. downregulates meiosis-specific CHK2 homolog, Mek1, which turn activates Ndt80 transcriptional activator exit. These support idea that is sensor ssDNAs activation DDR. Rfa1 also accelerates I delay induced zip1 mutant defective chromosome synapsis recombination, suggesting accumulation rather than triggers mutant.

Language: Английский

From conservation to adaptation: understanding the synaptonemal complex’s evolutionary dynamics DOI Creative Commons
S. M. Williams, R. Scott Hawley

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 93, P. 102349 - 102349

Published: April 17, 2025

The synaptonemal complex (SC) is structurally conserved across eukaryotes and essential for a proper progression of meiosis. Despite this conservation, SC protein sequences diverge drastically. In review, we explore findings on evolution, highlighting key differences commonalities among lineages like the Caenorhabditis Drosophila genera. We further known cases where its proteins adopt novel functional roles discuss why knowledge these could be important study canonical biology. existing studies demonstrate that work evolutionary biology in more diverse meiotic research organisms should play major role aiding our understanding structure functions.

Language: Английский

Citations

0
Temporal and Functional Relationship between Synaptonemal Complex Morphogenesis and Recombination during Meiosis DOI Open Access
Jasvinder S. Ahuja, Rima Sandhu,

Lingzhi Huang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 11, 2024

During prophase of meiosis I, programmed double strand breaks (DSBs) are processed into crossovers, a critical requirement for segregation homologous chromosomes (homologs) and genome haploidization in sexually reproducing organisms. Crossovers form via recombination close temporospatial association with morphogenesis the synaptonemal complex (SC), proteinaceous structure that connects paired homologs along their length during pachytene stage. Synapsis paradigm interplay between higher order chromosome DNA metabolism, yet temporal functional relationship remains poorly understood. Probing linkage these processes budding yeast, we show SC assembly is associated distinct threshold number unstable D-loops. The transition from bona fide paranemic D-loops to plectonemic DSB single end invasions (SEIs) completed midpachynema, when fully assembled. Double Holliday junctions (dHJs) at time desynapsis resolved crossovers diplonema. central element component Zip1 shepherds through three transitions, including first exchange second capture, as well dHJ resolution. mediates SEI formation independent its polymerization whereas precocious interferes junction Together, our findings indicate controls while assembled but also beyond disassembly, possibly by establishing spatial constraints sites.

Language: Английский

Citations

3
Genotype-specific differences in infertile men due to loss-of-function variants in M1AP or ZZS genes DOI Creative Commons
Nadja Rotte, Jessica E. M. Dunleavy,

Michelle D. Runkel

et al.

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

Abstract Male infertility has been linked to M1AP. In mice, M1AP interacts with the ZZS proteins SHOC1/TEX11/SPO16, promoting DNA class I crossover formation during meiosis. To determine whether and are involved in human male by recombination failure, we screened for biallelic/hemizygous loss-of-function (LoF) variants genes select men presumed protein deficiency ( N = 24). After in-depth characterisation of testicular phenotypes, identified gene-specific meiotic impairments: shared an early arrest. Men LoF exhibited a predominant metaphase arrest rare haploid round or even elongated spermatids. These differences were explained different failures: deficient function led incorrect synapsis homologous chromosomes, unrepaired double-strand breaks, incomplete recombination. Abolished reduced number intermediates crossover. Medically assisted reproduction resulted birth healthy child, offering possibility fatherhood . Our study establishes as important, but non-essential, functional enhancer

Language: Английский

Citations

0
Meiotic Cytokinesis in Saccharomyces cerevisiae: Spores That Just Need Closure DOI Creative Commons

Matthew Durant,

Xheni Mucelli,

Linda Huang

et al.

Journal of Fungi, Journal Year: 2024, Volume and Issue: 10(2), P. 132 - 132

Published: Feb. 6, 2024

In the budding yeast

Language: Английский

Citations

2
Agent-based modeling of nuclear chromosome ensembles identifies determinants of homolog pairing during meiosis DOI Creative Commons
Ariana Chriss,

G. Valentin Börner,

Shawn D. Ryan

et al.

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(5), P. e1011416 - e1011416

Published: May 13, 2024

During meiosis, pairing of homologous chromosomes (homologs) ensures the formation haploid gametes from diploid precursor cells, a prerequisite for sexual reproduction. Pairing during meiotic prophase I facilitates crossover recombination and homolog segregation ensuing reductional cell division. Mechanisms that ensure stable alignment in presence an excess non-homologous have remained elusive, but rapid chromosome movements appear to play role process. Apart attraction, provided by early intermediates recombination, dissociation associations also appears contribute pairing, as suggested detection pairing-defective mutants. Here, we developed agent-based model derived dynamics naturally occurring ensemble. The simulates unidirectional movements, well collision determined attractive repulsive forces arising close-range physical interactions. Chromosome number size movement velocity are identified key factors kinetics efficiency addition attraction. Dissociation interactions between may crowding homologs into limited nuclear area thus creating preconditions Incorporating natural lengths, accurately recapitulates observed wild-type mutant meiosis budding yeast, can be adapted dimensions sets other organisms.

Language: Английский

Citations

1
Mutational analysis of Mei5, a subunit of Mei5‐Sae3 complex, in Dmc1‐mediated recombination during yeast meiosis DOI Open Access

Stephen Mwaniki,

Priyanka Sawant,

Osaretin P. Osemwenkhae

et al.

Genes to Cells, Journal Year: 2024, Volume and Issue: 29(8), P. 650 - 666

Published: June 25, 2024

Interhomolog recombination in meiosis is mediated by the Dmc1 recombinase. The Mei5-Sae3 complex of Saccharomyces cerevisiae promotes assembly and functions with for homology-mediated repair meiotic DNA double-strand breaks. How facilitates remains poorly understood. In this study, we created characterized several mei5 mutants featuring amino acid substitutions basic residues. We found that Arg97 Mei5, conserved its ortholog, SFR1 (complex SWI5), RAD51 mediator, humans other organisms, critical formation Sae3 assembly. Moreover, substitution either Arg117 or Lys133 Ala Mei5 resulted production a C-terminal truncated protein during yeast meiosis. Notably, shorter Mei5-R117A was observed cells but not mitotic when expressed, suggesting unique regulation Dmc1-mediated posttranslational processing Mei5-Sae3.

Language: Английский

Citations

1
The deubiquitinase Usp7 in Drosophila melanogaster is required for synaptonemal complex maintenance DOI Creative Commons
Cathleen M. Lake, Jennifer M. Gardner,

Salam Briggs

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(36)

Published: Aug. 27, 2024

Meiosis is a form of cell division that essential to sexually reproducing organisms and therefore highly regulated. Each event meiosis must occur at the correct developmental stage ensure chromosomes are segregated properly during both meiotic divisions. One unique meiosis-specific structure tightly regulated in terms timing assembly disassembly synaptonemal complex (SC). While mechanism(s) for SC poorly understood Drosophila melanogaster , posttranslational modifications, including ubiquitination phosphorylation, known play role. Here, we identify role deubiquitinase Usp7 maintenance early prophase show its function independent recombination process. Using two usp7 shRNA constructs result different knockdown levels, have shown presence through early/mid-pachytene critical normal levels placement crossovers.

Language: Английский

Citations

1
Synaptonemal complex protects double-Holliday junctions during meiosis DOI Creative Commons

Shangming Tang,

Jennifer Koo,

Mohammad S. Pourhosseinzadeh

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 15, 2024

Chromosomal linkages formed through crossover recombination are essential for accurate segregation of homologous chromosomes during meiosis

Language: Английский

Citations

1
Keeping it safe: control of meiotic chromosome breakage DOI

Adhithi R. Raghavan,

Andreas Hochwagen

Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

1
Replication protein-A, RPA, plays a pivotal role in the maintenance of recombination checkpoint in yeast meiosis DOI Creative Commons

Arivarasan Sampathkumar,

Zhong Chen, Yuting Tang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 25, 2024

Abstract DNA double-strand breaks (DSBs) activate damage responses (DDRs) in both mitotic and meiotic cells. A single-stranded (ssDNA) binding protein, Replication protein-A (RPA) binds to the ssDNA formed at DSBs ATR/Mec1 kinase for response. Meiotic induce homologous recombination monitored by a DDR called checkpoint that blocks pachytene exit prophase I. In this study, we further characterized essential role of RPA maintenance during Saccharomyces cerevisiae meiosis. The depletion an subunit, Rfa1, recombination-defective dmc1 mutant, fully alleviates arrest with persistent unrepaired DSBs. decreases activity meiosis-specific CHK2 homolog, Mek1 kinase, which turn activates Ndt80 transcriptional regulator exit. These support idea is sensor ssDNAs activation DDR. Rfa1 also accelerates I delay zip1 mutant defective chromosome synapsis recombination, consistent notion accumulation rather than triggers mutant.

Language: Английский

Citations

1