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1.
PLoS Comput Biol ; 18(6): e1010252, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35696428

RESUMO

During meiosis, homologous chromosomes become associated side by side in a process known as homologous chromosome pairing. Pairing requires long range chromosome motion through a nucleus that is full of other chromosomes. It remains unclear how the cell manages to align each pair of chromosomes quickly while mitigating and resolving interlocks. Here, we use a coarse-grained molecular dynamics model to investigate how specific features of meiosis, including motor-driven telomere motion, nuclear envelope interactions, and increased nuclear size, affect the rate of pairing and the mitigation/resolution of interlocks. By creating in silico versions of three yeast strains and comparing the results of our model to experimental data, we find that a more distributed placement of pairing sites along the chromosome is necessary to replicate experimental findings. Active motion of the telomeric ends speeds up pairing only if binding sites are spread along the chromosome length. Adding a meiotic bouquet significantly speeds up pairing but does not significantly change the number of interlocks. An increase in nuclear size slows down pairing while greatly reducing the number of interlocks. Interestingly, active forces increase the number of interlocks, which raises the question: How do these interlocks resolve? Our model gives us detailed movies of interlock resolution events which we then analyze to build a step-by-step recipe for interlock resolution. In our model, interlocks must first translocate to the ends, where they are held in a quasi-stable state by a large number of paired sites on one side. To completely resolve an interlock, the telomeres of the involved chromosomes must come in close proximity so that the cooperativity of pairing coupled with random motion causes the telomeres to unwind. Together our results indicate that computational modeling of homolog pairing provides insight into the specific cell biological changes that occur during meiosis.


Assuntos
Pareamento Cromossômico , Meiose , Pareamento Cromossômico/genética , Meiose/genética , Membrana Nuclear , Saccharomyces cerevisiae/genética , Telômero/genética
2.
Sci Rep ; 12(1): 10597, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732879

RESUMO

The increasing human population demands an increase in crop yields that must be implemented through breeding programmes to ensure a more efficient and sustainable production of agro-food products. In the framework of breeding, genetic crosses are developed between cultivated species such as wheat and their relative species that are used as genetic donors to transfer desirable agronomic traits into the crop. Unfortunately, interspecific associations between chromosomes from the donor species and the cultivar are rare during meiosis, the process to produce gametes in organisms with sexual reproduction, hampering the transfer of genetic variability into wheat. In addition, little is known about how homologous (equivalent) chromosomes initiate interaction and recognition within the cell nucleus to enter meiosis. In this context, we aim to get insight into wheat chromatin structure, particularly the distribution of homologous chromosomes within the cell nucleus and their putative interactions in premeiotic stages to facilitate chromosome associations and recombination at the beginning of meiosis. Cytogenetics allows the study of both the structure and the behaviour of chromosomes during meiosis and is key in plant breeding. In this study we visualized an extra pair of barley homologous chromosomes in a wheat genetic background to study the spatial distribution, arrangements and interactions occurring exclusively between this pair of homologous chromosomes during premeiosis using fluorescence in situ hybridization (FISH). Our results suggest that homologous chromosomes can initiate interactions in premeiotic stages that could facilitate the processes of specific chromosome recognition and association occurring at the onset of meiosis.


Assuntos
Melhoramento Vegetal , Triticum , Pareamento Cromossômico/genética , Cromossomos , Hibridização in Situ Fluorescente , Meiose/genética , Triticum/genética
3.
Science ; 376(6599): eabh3104, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35549308

RESUMO

A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope through microtubules, driving chromosome homology searches. Telomere pulling toward the centrosome forms the "zygotene chromosomal bouquet." Here, we identified the "zygotene cilium" in oocytes. This cilium provides a cable system for the bouquet machinery and extends throughout the germline cyst. Using zebrafish mutants and live manipulations, we demonstrate that the cilium anchors the centrosome to counterbalance telomere pulling. The cilium is essential for bouquet and synaptonemal complex formation, oogenesis, ovarian development, and fertility. Thus, a cilium represents a conserved player in zebrafish and mouse meiosis, which sheds light on reproductive aspects in ciliopathies and suggests that cilia can control chromosomal dynamics.


Assuntos
Pareamento Cromossômico , Cílios , Oócitos , Oogênese , Ovário , Animais , Centrômero/genética , Centrômero/fisiologia , Pareamento Cromossômico/genética , Pareamento Cromossômico/fisiologia , Cílios/fisiologia , Feminino , Fertilidade/fisiologia , Camundongos , Morfogênese , Oócitos/crescimento & desenvolvimento , Oogênese/genética , Oogênese/fisiologia , Ovário/crescimento & desenvolvimento , Telômero/genética , Telômero/fisiologia , Peixe-Zebra/genética , Peixe-Zebra/fisiologia
4.
Nucleic Acids Res ; 50(10): 5617-5634, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35580048

RESUMO

Generation of haploid gametes depends on a modified version of homologous recombination in meiosis. Meiotic recombination is initiated by single-stranded DNA (ssDNA) ends originating from programmed DNA double-stranded breaks (DSBs) that are generated by the topoisomerase-related SPO11 enzyme. Meiotic recombination involves chromosomal synapsis, which enhances recombination-mediated DSB repair, and thus, crucially contributes to genome maintenance in meiocytes. Synapsis defects induce oocyte apoptosis ostensibly due to unrepaired DSBs that persist in asynaptic chromosomes. In mice, SPO11-deficient oocytes feature asynapsis, apoptosis and, surprisingly, numerous foci of the ssDNA-binding recombinase RAD51, indicative of DSBs of unknown origin. Hence, asynapsis is suggested to trigger apoptosis due to inefficient DSB repair even in mutants that lack programmed DSBs. By directly detecting ssDNAs, we discovered that RAD51 is an unreliable marker for DSBs in oocytes. Further, SPO11-deficient oocytes have fewer persistent ssDNAs than wild-type oocytes. These observations suggest that oocyte quality is safeguarded in mammals by a synapsis surveillance mechanism that can operate without persistent ssDNAs.


Assuntos
Pareamento Cromossômico , Endodesoxirribonucleases , Oócitos , Animais , Apoptose , Proteínas de Ciclo Celular/metabolismo , DNA , Quebras de DNA de Cadeia Dupla , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Mamíferos/genética , Meiose , Camundongos , Oócitos/citologia , Oócitos/metabolismo , Reparo de DNA por Recombinação
5.
Toxins (Basel) ; 14(3)2022 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-35324672

RESUMO

Cylindrospermopsin (CYN) is a cyanotoxin whose incidence has been increasing in the last decades. Due to its capacity to exert damage at different levels of the organism, it is considered a cytotoxin. Although the main target organ is the liver, recent studies indicate that CYN has potential toxic effects on the nervous system, both in vitro and in vivo. Thus, the aim of the present work was to study the effects of this cyanotoxin on neuronal viability and synaptic integrity in murine primary cultures of neurons exposed to environmentally relevant concentrations (0-1 µg/mL CYN) for 12, 24, and 48 h. The results demonstrate a concentration- and time-dependent decrease in cell viability; no cytotoxicity was detected after exposure to the cyanotoxin for 12 h, while all of the concentrations assayed decreased this parameter after 48 h. Furthermore, CYN was also demonstrated to exert damage at the synaptic level in a murine primary neuronal culture in a concentration- and time-dependent manner. These data highlight the importance of studying the neurotoxic properties of this cyanotoxin in different experimental models.


Assuntos
Toxinas Bacterianas , Uracila , Alcaloides , Animais , Toxinas Bacterianas/toxicidade , Pareamento Cromossômico , Camundongos , Neurônios , Uracila/toxicidade
6.
New Phytol ; 235(1): 157-172, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35322878

RESUMO

Meiosis is an essential reproductive process to create new genetic variation. During early meiosis, higher order chromosome organization creates a platform for meiotic processes to ensure the accuracy of recombination and chromosome segregation. However, little is known about the regulatory mechanisms underlying dynamic chromosome organization in plant meiosis. Here, we describe abnormal chromosome organization in zygotene1 (ACOZ1), which encodes a canonical F-box protein in maize. In acoz1 mutant meiocytes, chromosomes maintain a leptotene-like state and never compact to a zygotene-like configuration. Telomere bouquet formation and homologous pairing are also distorted and installation of synaptonemal complex ZYP1 protein is slightly defective. Loading of early recombination proteins RAD51 and DMC1 is unaffected, indicating that ACOZ1 is not required for double strand break formation or repair. However, crossover formation is severely disturbed. The ACOZ1 protein localizes on the boundary of chromatin, rather directly to chromosomes. Furthermore, we identified that ACOZ1 interacts with SKP1 through its C-terminus, revealing that it acts as a subunit of the SCF E3 ubiquitin/SUMO ligase complex. Overall, our results suggest that ACOZ1 functions independently from the core meiotic recombination pathway to influence crossover formation by controlling chromosome compaction during maize meiosis.


Assuntos
Proteínas F-Box , Zea mays , Pareamento Cromossômico , Segregação de Cromossomos/genética , Cromossomos , Proteínas F-Box/genética , Meiose , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Complexo Sinaptonêmico/metabolismo , Zea mays/genética , Zea mays/metabolismo
7.
Mol Biol Cell ; 33(5): ar37, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35274968

RESUMO

Homologous recombination (HR) is an essential meiotic process that contributes to the genetic variation of offspring and ensures accurate chromosome segregation. Recombination is facilitated by the formation and repair of programmed DNA double-strand breaks. These DNA breaks are repaired via recombination between maternal and paternal homologous chromosomes and a subset result in the formation of crossovers. HR and crossover formation is facilitated by synapsis of homologous chromosomes by a proteinaceous scaffold structure known as the synaptonemal complex (SC). Recent studies in yeast and worms have indicated that polo-like kinases (PLKs) regulate several events during meiosis, including DNA recombination and SC dynamics. Mammals express four active PLKs (PLK1-4), and our previous work assessing localization and kinase function in mouse spermatocytes suggested that PLK1 coordinates nuclear events during meiotic prophase. Therefore, we conditionally mutated Plk1 in early prophase spermatocytes and assessed stages of HR, crossover formation, and SC processes. Plk1 mutation resulted in increased RPA foci and reduced RAD51/DMC1 foci during zygonema, and an increase of both class I and class II crossover events. Furthermore, the disassembly of SC lateral elements was aberrant. Our results highlight the importance of PLK1 in regulating HR and SC disassembly during spermatogenesis.


Assuntos
Proteínas de Ciclo Celular , Recombinação Homóloga , Proteínas Proto-Oncogênicas , Espermatogênese , Complexo Sinaptonêmico , Animais , Proteínas de Ciclo Celular/genética , Pareamento Cromossômico , DNA , Masculino , Mamíferos , Meiose , Camundongos , Proteínas Proto-Oncogênicas/genética
8.
Elife ; 112022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35133274

RESUMO

DNA damage response mechanisms have meiotic roles that ensure successful gamete formation. While completion of meiotic double-strand break (DSB) repair requires the canonical RAD9A-RAD1-HUS1 (9A-1-1) complex, mammalian meiocytes also express RAD9A and HUS1 paralogs, RAD9B and HUS1B, predicted to form alternative 9-1-1 complexes. The RAD1 subunit is shared by all predicted 9-1-1 complexes and localizes to meiotic chromosomes even in the absence of HUS1 and RAD9A. Here, we report that testis-specific disruption of RAD1 in mice resulted in impaired DSB repair, germ cell depletion, and infertility. Unlike Hus1 or Rad9a disruption, Rad1 loss in meiocytes also caused severe defects in homolog synapsis, impaired phosphorylation of ATR targets such as H2AX, CHK1, and HORMAD2, and compromised meiotic sex chromosome inactivation. Together, these results establish critical roles for both canonical and alternative 9-1-1 complexes in meiotic ATR activation and successful prophase I completion.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Pareamento Cromossômico , Reparo do DNA , Meiose , Animais , Quebras de DNA de Cadeia Dupla , Proteínas de Ligação a DNA/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Transdução de Sinais , Testículo/metabolismo
9.
PLoS Genet ; 18(2): e1010041, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35192603

RESUMO

Histone methylation and demethylation play important roles in plant growth and development, but the involvement of histone demethylation during meiosis is poorly understood. Here we show that disruption of Arabidopsis thaliana INCREASE IN BONSAI METHYLATION 1 (IBM1) causes incomplete synapsis, chromosome entanglement and reduction of recombination during meiosis, leading to sterility. Interestingly, these ibm1 meiotic defects are rescued by mutations in either SUVH4/KYP or CMT3. Using transcriptomic analyses we show that mutation of IBM1 down-regulates thousands of genes expressed in meiocytes, and that expression of about 38% of these genes are restored to wild type levels in ibm1 cmt3 double mutants. Changes in the expression of 437 of these, including the ARABIDOPSIS MEI2-LIKE AML3-5 genes, are correlated with a significant reduction of gene body CHG methylation. Consistently, the aml3 aml4 aml5 triple have defects in synapsis and chromosome entanglement similar to ibm1. Genetic analysis shows that aml3 aml4 aml5 ibm1 quadruple mutants resembles the ibm1 single mutant. Strikingly, over expression of AML5 in ibm1 can partially rescue the ibm1 meiotic defects. Taken together, our results demonstrate that histone demethylase IBM1 is required for meiosis likely via coordinated regulation of meiocyte gene expression during meiosis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Pareamento Cromossômico/genética , Cromossomos/metabolismo , Metilação de DNA/genética , Expressão Gênica , Histona Desmetilases/genética , Histonas/genética , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Meiose/genética , Mutação , Recombinação Genética
10.
PLoS Genet ; 18(2): e1010040, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35130272

RESUMO

During meiotic prophase I, homologous chromosomes pair, synapse and recombine in a tightly regulated process that ensures the generation of genetically variable haploid gametes. Although the mechanisms underlying meiotic cell division have been well studied in model species, our understanding of the dynamics of meiotic prophase I in non-traditional model mammals remains in its infancy. Here, we reveal key meiotic features in previously uncharacterised marsupial species (the tammar wallaby and the fat-tailed dunnart), plus the fat-tailed mouse opossum, with a focus on sex chromosome pairing strategies, recombination and meiotic telomere homeostasis. We uncovered differences between phylogroups with important functional and evolutionary implications. First, sex chromosomes, which lack a pseudo-autosomal region in marsupials, had species specific pairing and silencing strategies, with implications for sex chromosome evolution. Second, we detected two waves of γH2AX accumulation during prophase I. The first wave was accompanied by low γH2AX levels on autosomes, which correlated with the low recombination rates that distinguish marsupials from eutherian mammals. In the second wave, γH2AX was restricted to sex chromosomes in all three species, which correlated with transcription from the X in tammar wallaby. This suggests non-canonical functions of γH2AX on meiotic sex chromosomes. Finally, we uncover evidence for telomere elongation in primary spermatocytes of the fat-tailed dunnart, a unique strategy within mammals. Our results provide new insights into meiotic progression and telomere homeostasis in marsupials, highlighting the importance of capturing the diversity of meiotic strategies within mammals.


Assuntos
Pareamento Cromossômico/fisiologia , Cromossomos Sexuais/fisiologia , Telômero/fisiologia , Animais , Macropodidae/genética , Marsupiais/genética , Meiose/genética , Meiose/fisiologia , Prófase Meiótica I/fisiologia , Gambás/genética , Cromossomos Sexuais/genética , Telômero/genética , Cromossomo X/genética , Cromossomo Y/genética
11.
J Exp Bot ; 73(11): 3386-3400, 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35201286

RESUMO

Homologs of PUTATIVE RECOMBINATION INITIATION DEFECT 1 (PRD1) are known to be essential for meiotic double-strand break (DSB) formation in mouse (Mus musculus), Arabidopsis, and rice (Oryza sativa). Recent research has shown that rice PRD1 also plays an unanticipated role in meiotic bipolar spindle assembly, revealing that PRD1 has multiple functions in plant meiosis. In this study, we characterize the meiotic function of PRD1 in maize (Zea mays; ZmPRD1). Our results show that Zmprd1 mutant plants display normal vegetative growth but have complete male and female sterility. Meiotic DSB formation is fully abolished in mutant meiocytes, leading to failure in homologous pairing, synapsis, and recombination. ZmPRD1 exhibits a different pattern of chromosome localization compared to its rice homologs. The ZmPRD1 protein interacts with several DSB-forming proteins, but does not directly interact with the kinetochore proteins REC8 and SGO1. Possibly as a result of this, there are no significant abnormalities of bipolar spindle assembly in Zmprd1 meiocytes. Overall, our results demonstrate that ZmPRD1 is essential for DSB formation and homologous recombination in maize meiosis. However, the recently-identified function of PRD1 in bipolar spindle assembly during rice meiosis is not conserved in maize.


Assuntos
Arabidopsis , Oryza , Animais , Arabidopsis/genética , Pareamento Cromossômico , Quebras de DNA de Cadeia Dupla , Recombinação Homóloga , Meiose , Camundongos , Oryza/genética , Oryza/metabolismo , Zea mays/genética , Zea mays/metabolismo
12.
Chromosome Res ; 30(1): 59-75, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35064347

RESUMO

Meiotic homologous chromosomes synapse and undergo crossing over (CO). In many eukaryotes, both synapsis and crossing over require the induction of double stranded breaks (DSBs) and subsequent repair via homologous recombination. In these organisms, two key proteins are recombinases RAD51 and DMC1. Recombinase-modulators HOP2 and MND1 assist RAD51 and DMC1 and also are required for synapsis and CO. We have investigated the hop2-1 phenotype in Arabidopsis during the segregation stages of both meiosis and mitosis. Despite a general lack of synapsis during prophase I, we observed extensive, stable interconnections between nonhomologous chromosomes in diploid hop2-1 nuclei in first and second meiotic divisions. Using γH2Ax as a marker of unrepaired DSBs, we detected γH2AX foci from leptotene through early pachytene but saw no foci from mid-pachytene onward. We conclude that the bridges seen from metaphase I onward are due to mis-repaired DSBs, not unrepaired ones. Examining haploids, we found that wild type haploids produce only univalents, but hop2-1 haploids like hop2-1 diploids have illegitimate connections stable enough to produce bridged chromosomes during segregation. Our results suggest that HOP2 has a significant active role in preventing repairs that use nonhomologous chromosomes during meiosis. We also found evidence that HOP2 plays a role in preventing illegitimate repair of radiation-induced DSBs in rapidly dividing petal cells. We conclude that HOP2 in Arabidopsis plays both a positive role in promoting synapsis and a separable role in preventing DSB repair using nonhomologous chromosomes. SIGNIFICANCE STATEMENT : The fidelity of homologous recombination (HR) during meiosis is essential to the production of viable gametes and for maintaining genome integrity in vegetative cells. HOP2 is an important protein for accurate meiotic HR in plants. We have found evidence of high levels of illegitimate repairs between nonhomologous chromosomes during meiosis and in irradiated petal cells in hop2-1 mutants, suggesting a role for HOP2 beyond its established role in synapsis and crossing over.


Assuntos
Arabidopsis , Arabidopsis/genética , Proteínas de Ciclo Celular/metabolismo , Pareamento Cromossômico , Cromossomos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Meiose , Rad51 Recombinase/genética
13.
Trends Genet ; 38(5): 419-421, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34776276

RESUMO

Polyploids must correctly segregate homologous chromosomes. We propose that this process is dictated not just by sequence similarity, but is also under strong genetic control that may vary between lineages. We also highlight how factors like partner availability and genome structure may influence sequence similarity needed for crossover formation.


Assuntos
Pareamento Cromossômico , Meiose , Pareamento Cromossômico/genética , Cromossomos/genética , Humanos , Poliploidia
14.
Genes Dev ; 36(1-2): 53-69, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969823

RESUMO

Meiotic recombination is triggered by programmed double-strand breaks (DSBs), a subset of these being repaired as crossovers, promoted by eight evolutionarily conserved proteins, named ZMM. Crossover formation is functionally linked to synaptonemal complex (SC) assembly between homologous chromosomes, but the underlying mechanism is unknown. Here we show that Ecm11, a SC central element protein, localizes on both DSB sites and sites that attach chromatin loops to the chromosome axis, which are the starting points of SC formation, in a way that strictly requires the ZMM protein Zip4. Furthermore, Zip4 directly interacts with Ecm11, and point mutants that specifically abolish this interaction lose Ecm11 binding to chromosomes and exhibit defective SC assembly. This can be partially rescued by artificially tethering interaction-defective Ecm11 to Zip4. Mechanistically, this direct connection ensuring SC assembly from CO sites could be a way for the meiotic cell to shut down further DSB formation once enough recombination sites have been selected for crossovers, thereby preventing excess crossovers. Finally, the mammalian ortholog of Zip4, TEX11, also interacts with the SC central element TEX12, suggesting a general mechanism.


Assuntos
Proteínas de Saccharomyces cerevisiae , Complexo Sinaptonêmico , Animais , Proteínas de Ciclo Celular/genética , Pareamento Cromossômico , Troca Genética , Mamíferos/genética , Meiose/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Complexo Sinaptonêmico/genética , Complexo Sinaptonêmico/metabolismo
15.
Genes Dev ; 36(1-2): 4-6, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35022326

RESUMO

During meiosis, a molecular program induces DNA double-strand breaks (DSBs) and their repair by homologous recombination. DSBs can be repaired with or without crossovers. ZMM proteins promote the repair toward crossover. The sites of DSB repair are also sites where the axes of homologous chromosomes are juxtaposed and stabilized, and where a structure called the synaptonemal complex initiates, providing further regulation of both DSB formation and repair. How crossover formation and synapsis initiation are linked has remained unknown. The study by Pyatnitskaya and colleagues (pp. 53-69) in this issue of Genes & Development highlights the central role of the Saccharomyces cerevisiae ZMM protein Zip4 in this process.


Assuntos
Troca Genética , Complexo Sinaptonêmico , Pareamento Cromossômico , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Meiose/genética
16.
Plant Physiol ; 188(2): 1210-1228, 2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-34927688

RESUMO

Changes in environmental temperature affect multiple meiotic processes in flowering plants. Polyploid plants derived from whole-genome duplication (WGD) have enhanced genetic plasticity and tolerance to environmental stress but face challenges in organizing and segregating doubled chromosome sets. In this study, we investigated the impact of increased environmental temperature on male meiosis in autotetraploid Arabidopsis (Arabidopsis thaliana). Under low to mildly increased temperatures (5°C-28°C), irregular chromosome segregation universally occurred in synthetic autotetraploid Columbia-0 (Col-0). Similar meiotic lesions occurred in autotetraploid rice (Oryza sativa L.) and allotetraploid canola (Brassica napus cv Westar), but not in evolutionarily derived hexaploid wheat (Triticum aestivum). At extremely high temperatures, chromosome separation and tetrad formation became severely disordered due to univalent formation caused by the suppression of crossing-over. We found a strong correlation between tetravalent formation and successful chromosome pairing, both of which were negatively correlated with temperature elevation, suggesting that increased temperature interferes with crossing-over predominantly by impacting homolog pairing. We also showed that loading irregularities of axis proteins ASY1 and ASY4 co-localize on the chromosomes of the syn1 mutant and the heat-stressed diploid and autotetraploid Col-0, revealing that heat stress affects the lateral region of synaptonemal complex (SC) by impacting the stability of the chromosome axis. Moreover, we showed that chromosome axis and SC in autotetraploid Col-0 are more sensitive to increased temperature than those in diploid Arabidopsis. Taken together, our data provide evidence suggesting that WGD negatively affects the stability and thermal tolerance of meiotic recombination in newly synthetic autotetraploid Arabidopsis.


Assuntos
Arabidopsis/genética , Pareamento Cromossômico/fisiologia , Recombinação Homóloga/fisiologia , Temperatura Alta/efeitos adversos , Meiose/fisiologia , Oryza/genética , Poliploidia , Arabidopsis/fisiologia , Produtos Agrícolas/genética , Produtos Agrícolas/fisiologia , Variação Genética , Genótipo , Resposta ao Choque Térmico/genética , Resposta ao Choque Térmico/fisiologia , Oryza/fisiologia
17.
Genes Genet Syst ; 97(1): 27-39, 2022 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34955498

RESUMO

Meiosis is a crucial process for spermatogenesis and oogenesis. Initiation of meiosis coincides with spermatocyte differentiation and is followed by meiotic prophase, a prolonged G2 phase that ensures the completion of numerous meiosis-specific chromosome events. During meiotic prophase, chromosomes are organized into axis-loop structures, which underlie meiosis-specific events such as meiotic recombination and homolog synapsis. In spermatocytes, meiotic prophase is accompanied by robust alterations of gene expression programs and chromatin status for subsequent sperm production. The mechanisms regulating meiotic initiation and subsequent meiotic prophase programs are enigmatic. Recently, we discovered MEIOSIN (Meiosis initiator), a DNA-binding protein that directs the switch from mitosis to meiosis. This review mainly focuses on how MEIOSIN is involved in meiotic initiation and the meiotic prophase program during spermatogenesis. Further, we discuss the downstream genes activated by MEIOSIN, which are crucial for meiotic prophase-specific events, from the viewpoint of chromosome dynamics and the gene expression program.


Assuntos
Meiose , Espermatogênese , Pareamento Cromossômico , Humanos , Masculino , Mitose , Espermatócitos/metabolismo , Espermatogênese/genética
18.
Genes (Basel) ; 12(12)2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34946793

RESUMO

Regulation of transcriptional activity during meiosis depends on the interrelated processes of recombination and synapsis. In eutherian mammal spermatocytes, transcription levels change during prophase-I, being low at the onset of meiosis but highly increased from pachytene up to the end of diplotene. However, X and Y chromosomes, which usually present unsynapsed regions throughout prophase-I in male meiosis, undergo a specific pattern of transcriptional inactivation. The interdependence of synapsis and transcription has mainly been studied in mammals, basically in mouse, but our knowledge in other unrelated phylogenetically species is more limited. To gain new insights on this issue, here we analyzed the relationship between synapsis and transcription in spermatocytes of the grasshopper Eyprepocnemis plorans. Autosomal chromosomes of this species achieve complete synapsis; however, the single X sex chromosome remains always unsynapsed and behaves as a univalent. We studied transcription in meiosis by immunolabeling with RNA polymerase II phosphorylated at serine 2 and found that whereas autosomes are active from leptotene up to diakinesis, the X chromosome is inactive throughout meiosis. This inactivation is accompanied by the accumulation of, at least, two repressive epigenetic modifications: H3 methylated at lysine 9 and H2AX phosphorylated at serine 139. Furthermore, we identified that X chromosome inactivation occurs in premeiotic spermatogonia. Overall, our results indicate: (i) transcription regulation in E. plorans spermatogenesis differs from the canonical pattern found in mammals and (ii) X chromosome inactivation is likely preceded by a process of heterochromatinization before the initiation of meiosis.


Assuntos
Gafanhotos/genética , Espermatogênese/genética , Inativação do Cromossomo X/genética , Cromossomo X/genética , Animais , Pareamento Cromossômico/genética , Epigênese Genética/genética , Feminino , Inativação Gênica/fisiologia , Histonas/genética , Lisina/genética , Masculino , Meiose/genética , Prófase Meiótica I/genética , RNA Polimerase II/genética , Espermatócitos/fisiologia , Cromossomo Y/genética
19.
Front Endocrinol (Lausanne) ; 12: 761249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721307

RESUMO

To achieve spermatogenesis in vitro, one of the most challenging processes to mimic is meiosis. Meiotic problems, like incomplete synapsis of the homologous chromosomes, or impaired homologous recombination, can cause failure of crossover formation and subsequent chromosome nondisjunction, eventually leading to aneuploid sperm. These meiotic events are therefore strictly monitored by meiotic checkpoints that initiate apoptosis of aberrant spermatocytes and lead to spermatogenic arrest. However, we recently found that, in vitro derived meiotic cells proceeded to the first meiotic division (MI) stage, despite displaying incomplete chromosome synapsis, no discernible XY-body and lack of crossover formation. We therefore optimized our in vitro culture system of meiosis from male germline stem cells (mGSCs) in order to achieve full chromosome synapsis, XY-body formation and meiotic crossovers. In comparison to previous culture system, the in vitro-generated spermatocytes were transferred after meiotic initiation to a second culture dish. This dish already contained a freshly plated monolayer of proliferatively inactivated immortalized Sertoli cells supporting undifferentiated mGSCs. In this way we aimed to simulate the multiple layers of germ cell types that support spermatogenesis in vivo in the testis. We found that in this optimized culture system, although independent of the undifferentiated mGSCs, meiotic chromosome synapsis was complete and XY body appeared normal. However, meiotic recombination still occurred insufficiently and only few meiotic crossovers were formed, leading to MI-spermatocytes displaying univalent chromosomes (paired sister chromatids). Therefore, considering that meiotic checkpoints are not necessarily fully functional in vitro, meiotic crossover formation should be closely monitored when mimicking gametogenesis in vitro to prevent generation of aneuploid gametes.


Assuntos
Pareamento Cromossômico/fisiologia , Cromossomos/fisiologia , Meiose/fisiologia , Aneuploidia , Animais , Azoospermia/congênito , Azoospermia/fisiopatologia , Diferenciação Celular/fisiologia , Linhagem Celular , Proliferação de Células/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Células de Sertoli/fisiologia , Espermatócitos/fisiologia , Espermatogênese/fisiologia , Espermatozoides/fisiologia , Testículo/fisiologia
20.
PLoS Genet ; 17(11): e1009598, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34762652

RESUMO

Meiotic homolog synapsis is essential to ensure accurate segregation of chromosomes during meiosis. In C. elegans, proper regulation of synapsis and a checkpoint that monitors synapsis relies on the spindle checkpoint components, Mad1 and Mad2, and Pairing Centers (PCs), cis-acting loci that interact with the nuclear envelope to mobilize chromosomes within the nucleus. Here, we test what specific functions of Mad1 and Mad2 are required to regulate and monitor synapsis. We find that a mutation that prevents Mad1's localization to the nuclear periphery abolishes the synapsis checkpoint but has no effect on Mad2's localization to the nuclear periphery or synapsis. By contrast, a mutation that prevents Mad1's interaction with Mad2 abolishes the synapsis checkpoint, delays synapsis and fails to localize Mad2 to the nuclear periphery. These data indicate that Mad1's primary role in regulating synapsis is through control of Mad2 and that Mad2 can bind other factors at the nuclear periphery. We also tested whether Mad2's ability to adopt a specific conformation associated with its activity during spindle checkpoint function is required for its role in meiosis. A mutation that prevents Mad2 from adopting its active conformer fails to localize to the nuclear periphery, abolishes the synapsis checkpoint and exhibits substantial defects in meiotic synapsis. Thus, Mad2, and its regulation by Mad1, is an important regulator of meiotic synapsis in C. elegans.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/metabolismo , Pareamento Cromossômico , Meiose , Animais , Núcleo Celular/metabolismo , Mutação , Ligação Proteica , Fuso Acromático/metabolismo
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