The survival of species depends on their ability to adapt to environmental changes. While organisms are known to activate common transcriptional pathways in response to temperature variations, the impact of temperature on recombination, a key source of genetic variability, remains largely unexplored. Previous studies in model species have shown that the frequency of recombination during meiotic prophase I can be influenced by extreme temperatures. Yet, it remains unclear whether this effect is also conserved in non-model vertebrates. In this study, we investigated the effect of temperature on recombination in the Guibé's ground gecko (Paroedura guibeae), an ectotherm species. We analyzed the formation of double-strand breaks (DSBs) and crossovers (COs) by immunolocalizing the meiotic proteins involved in these processes. Furthermore, we determined the frequency and chromosomal location of COs and the levels of CO interference (COI). Our findings show the presence of hyper-COs spermatocytes in individuals exposed to both high and low temperatures. Notably, this significant increase in COs was associated with a decrease in chromosome axis lengths and elevated levels of meiotic DSBs in later stages of prophase I. In conclusion, our results provide new insights into the effects of environmental temperatures on meiotic recombination in ectothermic species, underscoring the intricate interplay between environmental factors and genetic processes.

• MeSH
• crossing over (genetika) MeSH
• dvouřetězcové zlomy DNA MeSH
• ještěři * genetika   MeSH
• meióza genetika   MeSH
• profáze meiózy I genetika   MeSH
• rekombinace genetická * genetika   MeSH
• spermatocyty metabolismus   MeSH
• teplota MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and their synaptonemal complex (SC) mediated stabilization. Here, we investigate 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 impairs synapsis elongation without affecting homolog recognition, chromosome movement or SC maintenance. Epistasis analyses reveal previously unrecognized activities for HIM-17 in regulating homolog pairing and SC assembly in a partially overlapping manner with BRA-2. We show that removing bra-2 or him-17 restores nuclear clustering, recruitment of PLK-2 at the nuclear periphery, and abrogation of ectopic synapsis in htp-1 mutants, suggesting intact CHK-2-mediated signaling and presence of a barrier that prevents SC polymerization in the absence of homology. Our findings shed light on the regulatory mechanisms ensuring faithful pairing and synapsis.

• MeSH
• Caenorhabditis elegans * genetika   metabolismus   cytologie   MeSH
• meióza * genetika   fyziologie   MeSH
• mutace MeSH
• párování chromozomů * genetika   MeSH
• proteiny buněčného cyklu * metabolismus   genetika   MeSH
• proteiny Caenorhabditis elegans * metabolismus   genetika   MeSH
• synaptonemální komplex metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Htp-1 protein, C elegans MeSH Prohlížeč
• proteiny buněčného cyklu * MeSH
• proteiny Caenorhabditis elegans * MeSH

This study unveils a new catalytic crossover reaction of sulfinamides. Leveraging mild acid catalysis, the reaction demonstrates a high tolerance to structural variations, yielding equimolar products across diverse sulfinamide substrates. Notably, small sulfinamide libraries can be selectively oxidized to sulfonamides, providing a new platform for ligand optimization and discovery in medicinal chemistry. This crossover chemotype provides a new tool for high-throughput experimentation in discovery chemistry.

• Publikační typ
• časopisecké články MeSH

Meiotic recombination is of central importance for the proper segregation of homologous chromosomes, but also for creating genetic diversity. It is initiated by the formation of double-strand breaks (DSBs) in DNA catalysed by evolutionarily conserved Spo11, together with additional protein partners. Difficulties in purifying the Spo11 protein have limited the characterization of its biochemical properties and of its interactions with other DSB proteins. In this study, we have purified fragments of Spo11 and show for the first time that Spo11 can physically interact with Mre11 and modulates its DNA binding, bridging, and nuclease activities. The interaction of Mre11 with Spo11 requires its far C-terminal region, which is in line with the severe meiotic phenotypes of various mre11 mutations located at the C-terminus. Moreover, calibrated ChIP for Mre11 shows that Spo11 promotes Mre11 recruitment to chromatin, independent of DSB formation. A mutant deficient in Spo11 interaction severely reduces the association of Mre11 with meiotic chromatin. Consistent with the reduction of Mre11 foci in this mutant, it strongly impedes DSB formation, leading to spore death. Our data provide evidence that physical interaction between Spo11 and Mre11, together with end-bridging, promote normal recruitment of Mre11 to hotspots and DSB formation.

• MeSH
• chromatin * metabolismus   MeSH
• DNA vazebné proteiny metabolismus   genetika   MeSH
• dvouřetězcové zlomy DNA * MeSH
• endodeoxyribonukleasy * metabolismus   genetika   MeSH
• exodeoxyribonukleasy metabolismus   genetika   MeSH
• meióza * genetika   MeSH
• mutace MeSH
• Saccharomyces cerevisiae - proteiny * metabolismus   genetika   MeSH
• Saccharomyces cerevisiae cytologie   genetika   metabolismus   MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chromatin * MeSH
• DNA vazebné proteiny MeSH
• endodeoxyribonukleasy * MeSH
• exodeoxyribonukleasy MeSH
• meiotic recombination protein SPO11 MeSH Prohlížeč
• MRE11 protein, S cerevisiae MeSH Prohlížeč
• Saccharomyces cerevisiae - proteiny * MeSH
• Spo11 protein, S cerevisiae MeSH Prohlížeč

INTRODUCTION: Meiotic recombination is one of the most important processes of evolution and adaptation to environmental conditions. Even though there is substantial knowledge about proteins involved in the process, targeting specific DNA loci by the recombination machinery is not well understood. OBJECTIVES: This study aims to investigate a wheat recombination hotspot (H1) in comparison with a "regular" recombination site (Rec7) on the sequence and epigenetic level in conditions with functional and non-functional Ph1 locus. METHODS: The DNA sequence, methylation pattern, and recombination frequency were analyzed for the H1 and Rec7 in three mapping populations derived by crossing introgressive wheat line 8.1 with cv. Chinese Spring (with Ph1 and ph1 alleles) and cv. Tähti. RESULTS: The H1 and Rec7 loci are 1.586 kb and 2.538 kb long, respectively. High-density mapping allowed to delimit the Rec7 and H1 to 19 and 574 bp and 593 and 571 bp CO sites, respectively. A new method (ddPing) allowed screening recombination frequency in almost 66 thousand gametes. The screening revealed a 5.94-fold higher recombination frequency at the H1 compared to the Rec7. The H1 was also found out of the Ph1 control, similarly as gamete distortion. The recombination was strongly affected by larger genomic rearrangements but not by the SNP proximity. Moreover, chromatin markers for open chromatin and DNA hypomethylation were found associated with crossover occurrence except for the CHH methylation. CONCLUSION: Our results, for the first time, allowed study of wheat recombination directly on sequence, shed new light on chromatin landmarks associated with particular recombination sites, and deepened knowledge about role of the Ph1 locus in control of wheat recombination processes. The results are suggesting more than one recombination control pathway. Understanding this phenomenon may become a base for more efficient wheat genome manipulation, gene pool enrichment, breeding, and study processes of recombination itself.

• Klíčová slova
• Crossovers, DNA methylation, Hotspot, Ph1 locus, Recombination, Wheat,
• MeSH
• chromatin * genetika   MeSH
• chromozomy MeSH
• DNA MeSH
• pšenice * genetika   MeSH
• šlechtění rostlin MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chromatin * MeSH
• DNA MeSH

Hybrid sterility (HS) is an early postzygotic reproductive isolation mechanism observed in all sexually reproducing species. Infertility of hybrids prevents gene flow between incipient species and leads to speciation. While Drosophila studies have focused almost exclusively on the genic control of HS, two other model species, Mus musculus and budding yeast, provided the first experimental evidence of hybrid sterility governed by the nongenic effects of DNA sequence divergence. Here, we propose that the nongenic effect of increasing DNA divergence between closely related species may impair mutual recognition of homologous chromosomes and disrupt their synapsis. Unsynapsed or mispaired homologs can induce early meiotic arrest, or their random segregation can cause aneuploidy of spermatids and sperm cells. Impaired recognition of homologs may thus act as a universal chromosomal checkpoint contributing to the complexity of genetic control of HS. Chromosomal HS controlled by the Prdm9 gene in mice and HS driven by the mismatch repair machinery in yeast are currently the most advanced examples of chromosomal homology search-based HS. More focus on the cellular and molecular phenotypes of meiosis will be needed to further validate the role of homolog recognition in hybrid sterility and speciation.

• Klíčová slova
• Prdm9, antirecombination, chromosomal sterility, meiotic pairing, reproductive isolation, speciation,
• MeSH
• chromozomy MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• hybridizace genetická MeSH
• infertilita * genetika   MeSH
• lidé MeSH
• meióza MeSH
• mužská infertilita * genetika   MeSH
• myši MeSH
• Saccharomyces cerevisiae genetika   MeSH
• semena rostlinná MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• PRDM9 protein, human MeSH Prohlížeč
• prdm9 protein, mouse MeSH Prohlížeč

Meiotic chromosome segregation relies on programmed DNA double-strand break induction. These are in turn repaired by homologous recombination, generating physical attachments between the parental chromosomes called crossovers. A subset of breaks yields recombinant outcomes, while crossover-independent mechanisms repair the majority of lesions. The balance between different repair pathways is crucial to ensure genome integrity. We show that Caenorhabditis elegans BRC-1/BRCA1-BRD-1/BARD1 and PARG-1/PARG form a complex in vivo, essential for accurate DNA repair in the germline. Simultaneous depletion of BRC-1 and PARG-1 causes synthetic lethality due to reduced crossover formation and impaired break repair, evidenced by hindered RPA-1 removal and presence of aberrant chromatin bodies in diakinesis nuclei, whose formation depends on spo-11 function. These factors undergo a similar yet independent loading in developing oocytes, consistent with operating in different pathways. Abrogation of KU- or Theta-mediated end joining elicits opposite effects in brc-1; parg-1 doubles, suggesting a profound impact in influencing DNA repair pathway choice by BRC-1-PARG-1. Importantly, lack of PARG-1 catalytic activity suppresses untimely accumulation of RAD-51 foci in brc-1 mutants but is only partially required for fertility. Our data show that BRC-1/BRD-1-PARG-1 joint function is essential for genome integrity in meiotic cells by regulating multiple DNA repair pathways.

• MeSH
• Caenorhabditis elegans genetika   MeSH
• DNA vazebné proteiny * metabolismus   MeSH
• dvouřetězcové zlomy DNA MeSH
• gametogeneze MeSH
• meióza MeSH
• oprava DNA * MeSH
• proteiny aktivující GTPasu * metabolismus   MeSH
• proteiny Caenorhabditis elegans * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• BRC-1 protein, C elegans MeSH Prohlížeč
• BRC-2 protein, C elegans MeSH Prohlížeč
• DNA vazebné proteiny * MeSH
• proteiny aktivující GTPasu * MeSH
• proteiny Caenorhabditis elegans * MeSH

Generation of functional gametes is accomplished through a multilayered and finely orchestrated succession of events during meiotic progression. In the Caenorhabditis elegans germline, the HORMA-domain-containing protein HTP-3 plays pivotal roles for the establishment of chromosome axes and the efficient induction of programmed DNA double-strand breaks, both of which are crucial for crossover formation. Double-strand breaks allow for accurate chromosome segregation during the first meiotic division and therefore are an essential requirement for the production of healthy gametes. Phosphorylation-dependent regulation of HORMAD protein plays important roles in controlling meiotic chromosome behavior. Here, we document a phospho-site in HTP-3 at Serine 285 that is constitutively phosphorylated during meiotic prophase I. pHTP-3S285 localization overlaps with panHTP-3 except in nuclei undergoing physiological apoptosis, in which pHTP-3 is absent. Surprisingly, we observed that phosphorylation of HTP-3 at S285 is independent of the canonical kinases that control meiotic progression in nematodes. During meiosis, the htp-3(S285A) mutant displays accelerated RAD-51 turnover, but no other meiotic abnormalities. Altogether, these data indicate that the Ser285 phosphorylation is independent of canonical meiotic protein kinases and does not regulate HTP-3-dependent meiotic processes. We propose a model wherein phosphorylation of HTP-3 occurs through noncanonical or redundant meiotic kinases and/or is likely redundant with additional phospho-sites for function in vivo.

• Klíčová slova
• Caenorhabditis elegans meiosis, HORMA-domain proteins, HTP-3,
• MeSH
• Caenorhabditis elegans genetika   metabolismus   MeSH
• fosforylace MeSH
• meióza * MeSH
• proteiny buněčného cyklu genetika   MeSH
• proteiny Caenorhabditis elegans * metabolismus   MeSH
• segregace chromozomů MeSH
• serin metabolismus   MeSH
• synaptonemální komplex metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• proteiny buněčného cyklu MeSH
• proteiny Caenorhabditis elegans * MeSH
• serin MeSH

A sudden shift in environment or cellular context necessitates rapid adaptation. A dramatic example is genome duplication, which leads to polyploidy. In such situations, the waiting time for new mutations might be prohibitive; theoretical and empirical studies suggest that rapid adaptation will largely rely on standing variation already present in source populations. Here, we investigate the evolution of meiosis proteins in Arabidopsis arenosa, some of which were previously implicated in adaptation to polyploidy, and in a diploid, habitat. A striking and unexplained feature of prior results was the large number of amino acid changes in multiple interacting proteins, especially in the relatively young tetraploid. Here, we investigate whether selection on meiosis genes is found in other lineages, how the polyploid may have accumulated so many differences, and whether derived variants were selected from standing variation. We use a range-wide sample of 145 resequenced genomes of diploid and tetraploid A. arenosa, with new genome assemblies. We confirmed signals of positive selection in the polyploid and diploid lineages they were previously reported in and find additional meiosis genes with evidence of selection. We show that the polyploid lineage stands out both qualitatively and quantitatively. Compared with diploids, meiosis proteins in the polyploid have more amino acid changes and a higher proportion affecting more strongly conserved sites. We find evidence that in tetraploids, positive selection may have commonly acted on de novo mutations. Several tests provide hints that coevolution, and in some cases, multinucleotide mutations, might contribute to rapid accumulation of changes in meiotic proteins.

• Klíčová slova
• coevolution, de novo mutations, meiosis, polyploidy, standing variation,
• MeSH
• Arabidopsis genetika   MeSH
• biologická adaptace genetika   MeSH
• koevoluce MeSH
• meióza genetika   MeSH
• molekulární evoluce * MeSH
• mutace MeSH
• tetraploidie * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Poly(ADP-ribosyl)ation is a reversible post-translational modification synthetized by ADP-ribose transferases and removed by poly(ADP-ribose) glycohydrolase (PARG), which plays important roles in DNA damage repair. While well-studied in somatic tissues, much less is known about poly(ADP-ribosyl)ation in the germline, where DNA double-strand breaks are introduced by a regulated program and repaired by crossover recombination to establish a tether between homologous chromosomes. The interaction between the parental chromosomes is facilitated by meiotic specific adaptation of the chromosome axes and cohesins, and reinforced by the synaptonemal complex. Here, we uncover an unexpected role for PARG in coordinating the induction of meiotic DNA breaks and their homologous recombination-mediated repair in Caenorhabditis elegans. PARG-1/PARG interacts with both axial and central elements of the synaptonemal complex, REC-8/Rec8 and the MRN/X complex. PARG-1 shapes the recombination landscape and reinforces the tightly regulated control of crossover numbers without requiring its catalytic activity. We unravel roles in regulating meiosis, beyond its enzymatic activity in poly(ADP-ribose) catabolism.

• MeSH
• buněčné jádro metabolismus   MeSH
• Caenorhabditis elegans genetika   metabolismus   MeSH
• DNA metabolismus   MeSH
• dvouřetězcové zlomy DNA * MeSH
• glykosidhydrolasy genetika   metabolismus   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• oprava DNA fyziologie   MeSH
• poly-ADP-ribosylace MeSH
• polyadenosindifosfátribosa metabolismus   MeSH
• posttranslační úpravy proteinů MeSH
• proteiny Caenorhabditis elegans genetika   metabolismus   MeSH
• zárodečné buňky MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DNA MeSH
• glykosidhydrolasy MeSH
• jaderné proteiny MeSH
• poly ADP-ribose glycohydrolase MeSH Prohlížeč
• polyadenosindifosfátribosa MeSH
• proteiny Caenorhabditis elegans MeSH
• SYP-1 protein, C elegans MeSH Prohlížeč