RNF212B E3 ligase is essential for crossover designation and maturation during male and female meiosis in the mouse DOI Creative Commons
Yazmine B. Condezo, Raquel Sainz-Urruela, Laura Gómez-H

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(25)

Published: June 12, 2024

Meiosis, a reductional cell division, relies on precise initiation, maturation, and resolution of crossovers (COs) during prophase I to ensure the accurate segregation homologous chromosomes metaphase I. This process is regulated by interplay RING-E3 ligases such as RNF212 HEI10 in mammals. In this study, we functionally characterized recently identified ligase, RNF212B. RNF212B colocalizes interacts with RNF212, forming foci along from zygonema onward synapsis-dependent DSB-independent manner. These consolidate into larger at maturing COs, colocalizing HEI10, CNTD1, MLH1 late pachynema. Genetically, formation depends Rnf212 but not Msh4 , Hei10, Cntd1 while unloading end pachynema dependent Hei10 . Mice lacking RNF212B, or expressing an inactive protein, exhibit modest synapsis defects, reduction localization pro-CO factors (MSH4, TEX11, RPA, MZIP2) absence CO-intermediates (MLH1). loss most COs diakinesis results mostly univalent chromosomes. Double mutants for Rnf212b identical phenotype that single mutants, double heterozygous demonstrate dosage-dependent CO number, indicating functional between paralogs. SUMOylome analysis testes pull-down Sumo- Ubiquitin-tagged HeLa cells, suggest E3-ligase Ubiquitin activity, serving crucial factor maturation. Thus, play vital, yet overlapping roles, ensuring homeostasis through their distinct E3 ligase activities.

Language: Английский

Distinct and interdependent functions of three RING proteins regulate recombination during mammalian meiosis DOI Creative Commons
Masaru Ito, Yan Yun, Dhananjaya S. Kulkarni

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(2)

Published: Jan. 6, 2025

During meiosis, each pair of homologous chromosomes becomes connected by at least one crossover, as required for accurate segregation, and adjacent crossovers are widely separated thereby limiting total numbers. In coarsening models, this crossover patterning results from nascent recombination sites competing to accrue a pro-crossover RING-domain protein (COR) that diffuses between synapsed chromosomes. Here, we delineate the localization dynamics three mammalian CORs in mouse determine their interdependencies. RNF212, HEI10, newest member RNF212B show divergent spatiotemporal along chromosomes, including profound differences spermatocytes oocytes, not easily reconciled elementary models. Contrasting mutant phenotypes genetic requirements indicate RNF212B, HEI10 play distinct but interdependent functions regulating meiotic coordinating events prophase-I integrating signals DNA breaks, homolog synapsis, cell-cycle, incipient sites.

Language: Английский

Citations

1
Improved synapsis dynamics accompany meiotic stability in Arabidopsis arenosa autotetraploids DOI Creative Commons
Adrián Gonzalo, Aditya R. Nayak, Kirsten Bomblies

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Abstract During meiosis, the correct pairing, synapsis, and recombination of homologous chromosome pairs is critical for fertility sexual eukaryotes. These processes are challenged in polyploids, which possess additional copies each chromosome. Polyploidy thus provides a unique context to study how evolution can modify meiotic programs response challenges. We previously observed that Arabidopsis arenosa newly formed (neo-)polyploids, synapsis defects precede chromosomes associating aberrant multivalent univalent configurations. Here we dynamics genotypes with varying levels stability ask whether efficient synaptic progression key component evolving stable tetraploid meiosis. develop method quantify using foci pro-crossover factor HEI10 as reference. initially appears at many small loci before accumulating only crossover sites. In diploids, this transition begins while there still significant asynapsis, quickly declines accumulation fewer progresses. neo-tetraploids, suboptimal elongation initiation sites, perhaps defective precedes stalling onset accumulation. established tetraploids, when asynapsis minimal, suggesting an enhanced HEI10/synapsis co-dynamic (even compared diploids). Hybrids generated by crossing neo- tetraploids exhibit intermediate phenotypes. find extent correlates positively numbers, well higher frequency multivalents univalent, disturb segregation. Our work supports hypothesis improving efficiency important polyploid stability. Significance Statement pair subsequently form synaptonemal complex, maturation DNA events. How formation coordinated where multiple sets complicate pair-wise interactions, remains unclear. Leveraging ‘developmental clock,’ quantified new . Synapsis severely compromised ones it more even than diploids. Notably, correlated excess crossovers, compromises connecting connect homologs multivalents. findings highlight polyploids.

Language: Английский

Citations

0
Improved synapsis dynamics accompany meiotic stability in Arabidopsis arenosa autotetraploids DOI Creative Commons
Adrián Gonzalo, Aditya R. Nayak, Kirsten Bomblies

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(19)

Published: May 7, 2025

During meiosis, the correct pairing, synapsis, and recombination of homologous chromosome pairs is critical for fertility sexual eukaryotes. These processes are challenged in polyploids, which possess additional copies each chromosome. Polyploidy thus provides a unique context to study how evolution can modify meiotic programs response challenges. We previously observed that newly formed (neo-)polyploids Arabidopsis arenosa , synapsis defects precede chromosomes associating aberrant multivalent univalent configurations. Here, we dynamics genotypes with varying levels stability ask whether efficient synaptic progression key component evolving stable tetraploid meiosis. develop method quantify using foci pro-crossover factor HEI10 as reference. initially appears at many small before accumulating only crossover sites. In diploids, this transition begins while significant asynapsis still present, though it quickly declines accumulates fewer foci. neo-tetraploids, suboptimal elongation initiation sites stalled perhaps due defective occurs onset accumulation. established tetraploids, accumulation when near complete, suggesting enhanced HEI10/synapsis codynamics (even compared diploids). Hybrids generated by crossing neo- tetraploids exhibit intermediate phenotypes. find extent correlates positively numbers, frequency multivalents univalents, disturb segregation. Our work supports hypothesis improving efficiency important polyploid stability.

Language: Английский

Citations

0
RNF212B E3 ligase is essential for crossover designation and maturation during male and female meiosis in the mouse DOI Creative Commons
Yazmine B. Condezo, Raquel Sainz-Urruela, Laura Gómez-H

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(25)

Published: June 12, 2024

Meiosis, a reductional cell division, relies on precise initiation, maturation, and resolution of crossovers (COs) during prophase I to ensure the accurate segregation homologous chromosomes metaphase I. This process is regulated by interplay RING-E3 ligases such as RNF212 HEI10 in mammals. In this study, we functionally characterized recently identified ligase, RNF212B. RNF212B colocalizes interacts with RNF212, forming foci along from zygonema onward synapsis-dependent DSB-independent manner. These consolidate into larger at maturing COs, colocalizing HEI10, CNTD1, MLH1 late pachynema. Genetically, formation depends Rnf212 but not Msh4 , Hei10, Cntd1 while unloading end pachynema dependent Hei10 . Mice lacking RNF212B, or expressing an inactive protein, exhibit modest synapsis defects, reduction localization pro-CO factors (MSH4, TEX11, RPA, MZIP2) absence CO-intermediates (MLH1). loss most COs diakinesis results mostly univalent chromosomes. Double mutants for Rnf212b identical phenotype that single mutants, double heterozygous demonstrate dosage-dependent CO number, indicating functional between paralogs. SUMOylome analysis testes pull-down Sumo- Ubiquitin-tagged HeLa cells, suggest E3-ligase Ubiquitin activity, serving crucial factor maturation. Thus, play vital, yet overlapping roles, ensuring homeostasis through their distinct E3 ligase activities.

Language: Английский

Citations

3