Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 19.241
Filtrar
1.
Nat Commun ; 11(1): 5191, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060587

RESUMO

In grasses, phased small interfering RNAs (phasiRNAs), 21- or 24-nucleotide (nt) in length, are predominantly expressed in anthers and play a role in regulating male fertility. However, their targets and mode of action on the targets remain unknown. Here we profile phasiRNA expression in premeiotic and meiotic spikelets as well as in purified male meiocytes at early prophase I, tetrads and microspores in rice. We show that 21-nt phasiRNAs are most abundant in meiocytes at early prophase I while 24-nt phasiRNAs are more abundant in tetrads and microspores. By performing highly sensitive degradome sequencing, we find that 21-nt phasiRNAs direct target mRNA cleavage in male germ cells, especially in meiocytes at early prophase I. These targets include 435 protein-coding genes and 71 transposons that show an enrichment for carbohydrate biosynthetic and metabolic pathways. Our study provides strong evidence that 21-nt phasiRNAs act in a target-cleavage mode and may facilitate the progression of meiosis by fine-tuning carbohydrate biosynthesis and metabolism in male germ cells.


Assuntos
Células Germinativas/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , RNA Mensageiro/metabolismo , RNA de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Meiose/fisiologia , Nucleotídeos , Oryza/embriologia , Oryza/genética , Proteínas de Plantas/genética , RNA Replicase/metabolismo , RNA de Plantas/genética , RNA Interferente Pequeno/metabolismo , Transcriptoma
2.
Nat Commun ; 11(1): 4917, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004802

RESUMO

Maternal mRNA clearance is an essential process that occurs during maternal-to-zygotic transition (MZT). However, the dynamics, functional importance, and pathological relevance of maternal mRNA decay in human preimplantation embryos have not yet been analyzed. Here we report the zygotic genome activation (ZGA)-dependent and -independent maternal mRNA clearance processes during human MZT and demonstrate that subgroups of human maternal transcripts are sequentially removed by maternal (M)- and zygotic (Z)-decay pathways before and after ZGA. Key factors regulating M-decay and Z-decay pathways in mouse have similar expression pattern during human MZT, suggesting that YAP1-TEAD4 transcription activators, TUT4/7-mediated mRNA 3'-oligouridylation, and BTG4/CCR4-NOT-induced mRNA deadenylation may also be involved in the regulation of human maternal mRNA stability. Decreased expression of these factors and abnormal accumulation of maternal transcripts are observed in the development-arrested embryos of patients who seek assisted reproduction. Defects of M-decay and Z-decay are detected with high incidence in embryos that are arrested at the zygote and 8-cell stages, respectively. In addition, M-decay is not found to be affected by maternal TUBB8 mutations, although these mutations cause meiotic cell division defects and zygotic arrest, which indicates that mRNA decay is regulated independent of meiotic spindle assembly. Considering the correlations between maternal mRNA decay defects and early developmental arrest of in vitro fertilized human embryos, M-decay and Z-decay pathway activities may contribute to the developmental potential of human preimplantation embryos.


Assuntos
Blastocisto/metabolismo , Desenvolvimento Embrionário/fisiologia , Estabilidade de RNA/fisiologia , RNA Mensageiro Estocado/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Animais , Técnicas de Cultura Embrionária , Feminino , Fertilização In Vitro/métodos , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Masculino , Meiose/genética , Camundongos , Mutação , Oócitos/metabolismo , Cultura Primária de Células , RNA-Seq , Tubulina (Proteína)/genética , Zigoto/metabolismo
3.
PLoS Genet ; 16(9): e1009001, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886661

RESUMO

During meiosis, diploid organisms reduce their chromosome number by half to generate haploid gametes. This process depends on the repair of double strand DNA breaks as crossover recombination events between homologous chromosomes, which hold homologs together to ensure their proper segregation to opposite spindle poles during the first meiotic division. Although most organisms are limited in the number of crossovers between homologs by a phenomenon called crossover interference, the consequences of excess interfering crossovers on meiotic chromosome segregation are not well known. Here we show that extra interfering crossovers lead to a range of meiotic defects and we uncover mechanisms that counteract these errors. Using chromosomes that exhibit a high frequency of supernumerary crossovers in Caenorhabditis elegans, we find that essential chromosomal structures are mispatterned in the presence of multiple crossovers, subjecting chromosomes to improper spindle forces and leading to defects in metaphase alignment. Additionally, the chromosomes with extra interfering crossovers often exhibited segregation defects in anaphase I, with a high incidence of chromatin bridges that sometimes created a tether between the chromosome and the first polar body. However, these anaphase I bridges were often able to resolve in a LEM-3 nuclease dependent manner, and chromosome tethers that persisted were frequently resolved during Meiosis II by a second mechanism that preferentially segregates the tethered sister chromatid into the polar body. Altogether these findings demonstrate that excess interfering crossovers can severely impact chromosome patterning and segregation, highlighting the importance of limiting the number of recombination events between homologous chromosomes for the proper execution of meiosis.


Assuntos
Segregação de Cromossomos/genética , Troca Genética/genética , Meiose/genética , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Cromátides/genética , Cromatina/genética , Posicionamento Cromossômico/genética , Cromossomos/genética , Quebras de DNA de Cadeia Dupla , Endodesoxirribonucleases/genética , Recombinação Genética
4.
Elife ; 92020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32936074

RESUMO

Three independent studies show that a protein called ZCWPW1 is able to recognize the histone modifications that initiate the recombination of genetic information during meiosis.


Assuntos
Quebras de DNA de Cadeia Dupla , Histonas , Animais , DNA , Reparo do DNA , Epigênese Genética , Masculino , Meiose , Camundongos , Leitura
5.
PLoS Genet ; 16(9): e1009048, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32931493

RESUMO

During meiotic prophase, sister chromatids are organized into axial element (AE), which underlies the structural framework for the meiotic events such as meiotic recombination and homolog synapsis. HORMA domain-containing proteins (HORMADs) localize along AE and play critical roles in the regulation of those meiotic events. Organization of AE is attributed to two groups of proteins: meiotic cohesins REC8 and RAD21L; and AE components SYCP2 and SYCP3. It has been elusive how these chromosome structural proteins contribute to the chromatin loading of HORMADs prior to AE formation. Here we newly generated Sycp2 null mice and showed that initial chromatin loading of HORMAD1 was mediated by meiotic cohesins prior to AE formation. HORMAD1 interacted not only with the AE components SYCP2 and SYCP3 but also with meiotic cohesins. Notably, HORMAD1 interacted with meiotic cohesins even in Sycp2-KO, and localized along cohesin axial cores independently of the AE components SYCP2 and SYCP3. Hormad1/Rad21L-double knockout (dKO) showed more severe defects in the formation of synaptonemal complex (SC) compared to Hormad1-KO or Rad21L-KO. Intriguingly, Hormad1/Rec8-dKO but not Hormad1/Rad21L-dKO showed precocious separation of sister chromatid axis. These findings suggest that meiotic cohesins REC8 and RAD21L mediate chromatin loading and the mode of action of HORMAD1 for synapsis during early meiotic prophase.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Animais , Cromátides/genética , Cromátides/metabolismo , Cromatina/metabolismo , Cromossomos/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Masculino , Meiose/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Nucleares/genética , Fosfoproteínas/genética , Prófase/genética , Espermatócitos/metabolismo , Complexo Sinaptonêmico/metabolismo
6.
J Biomed Nanotechnol ; 16(5): 659-671, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919486

RESUMO

Nano-titanium dioxide (nano-TiO2) has been widely used in food and cosmetic industries, and the medical sector. However, nano-TiO2 is potentially toxic to the reproductive system. Previous research has shown that nano-TiO2 can reduce sperm concentration but do not yet known whether this effect occurs because of dysfunctional meiosis in spermatogenic cells. In the present paper, we demonstrate that Nano-TiO2 can penetrate through the blood-testis barrier of a mouse model and enter the testicular tissue, thus causing damage to the testis and epididymis. This reduced the number of developing sperm; we demonstrated that the mechanism underlying this effect was the inhibition or destruction of meiosis in spermatogenic cells, particularly during meiosis I. We also found that the inhibition of meiosis I caused by nano-TiO2 exposure was related to dysfunctional meiosis and that the abnormal expression of meiosis-related factors. Therefore, our data demonstrate that nano-TiO2 reduces sperm concentration by disrupting meiosis and related signaling pathways.


Assuntos
Nanopartículas , Animais , Masculino , Meiose , Camundongos , Transdução de Sinais , Espermatozoides , Titânio
7.
Nat Commun ; 11(1): 4486, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900989

RESUMO

Centromeres are epigenetically determined nuclear domains strictly required for chromosome segregation and genome stability. However, the mechanisms regulating centromere and kinetochore chromatin modifications are not known. Here, we demonstrate that LSH is enriched at meiotic kinetochores and its targeted deletion induces centromere instability and abnormal chromosome segregation. Superresolution chromatin analysis resolves LSH at the inner centromere and kinetochores during oocyte meiosis. LSH knockout pachytene oocytes exhibit reduced HDAC2 and DNMT-1. Notably, mutant oocytes show a striking increase in histone H3 phosphorylation at threonine 3 (H3T3ph) and accumulation of major satellite transcripts in both prophase-I and metaphase-I chromosomes. Moreover, knockout oocytes exhibit centromere fusions, ectopic kinetochore formation and abnormal exchange of chromatin fibers between paired bivalents and asynapsed chromosomes. Our results indicate that loss of LSH affects the levels and chromosomal localization of H3T3ph and provide evidence that, by maintaining transcriptionally repressive heterochromatin, LSH may be essential to prevent deleterious meiotic recombination events at repetitive centromeric sequences.


Assuntos
DNA Helicases/metabolismo , Meiose/fisiologia , Oócitos/citologia , Oócitos/metabolismo , Animais , Centrômero/genética , Centrômero/metabolismo , DNA Helicases/deficiência , DNA Helicases/genética , Feminino , Histonas/metabolismo , Cinetocoros/metabolismo , Masculino , Meiose/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Transcrição Genética
9.
Mutat Res ; 785: 108320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32800274

RESUMO

It is well established that maternal age is associated with a rapid decline in the production of healthy and high-quality oocytes resulting in reduced fertility in women older than 35 years of age. In particular, chromosome segregation errors during meiotic divisions are increasingly common and lead to the production of oocytes with an incorrect number of chromosomes, a condition known as aneuploidy. When an aneuploid oocyte is fertilized by a sperm it gives rise to an aneuploid embryo that, except in rare situations, will result in a spontaneous abortion. As females advance in age, they are at higher risk of infertility, miscarriage, or having a pregnancy affected by congenital birth defects such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Turner syndrome (monosomy X). Here, we review the potential molecular mechanisms associated with increased chromosome segregation errors during meiosis as a function of maternal age. Our review shows that multiple exogenous and endogenous factors contribute to the age-related increase in oocyte aneuploidy. Specifically, the weight of evidence indicates that recombination failure, cohesin deterioration, spindle assembly checkpoint (SAC) disregulation, abnormalities in post-translational modification of histones and tubulin, and mitochondrial dysfunction are the leading causes of oocyte aneuploidy associated with maternal aging. There is also growing evidence that dietary and other bioactive interventions may mitigate the effect of maternal aging on oocyte quality and oocyte aneuploidy, thereby improving fertility outcomes. Maternal age is a major concern for aneuploidy and genetic disorders in the offspring in the context of an increasing proportion of mothers having children at increasingly older ages. A better understanding of the mechanisms associated with maternal aging leading to aneuploidy and of intervention strategies that may mitigate these detrimental effects and reduce its occurrence are essential for preventing abnormal reproductive outcomes in the human population.


Assuntos
Aneuploidia , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Segregação de Cromossomos/genética , Anormalidades Congênitas/genética , Idade Materna , Anormalidades Congênitas/prevenção & controle , Feminino , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Meiose/genética , Mitocôndrias/fisiologia , Oócitos/fisiologia
10.
PLoS One ; 15(8): e0236285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841250

RESUMO

Characterizing meiotic recombination rates across the genomes of nonhuman primates is important for understanding the genetics of primate populations, performing genetic analyses of phenotypic variation and reconstructing the evolution of human recombination. Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primates in biomedical research. We constructed a high-resolution genetic map of the rhesus genome based on whole genome sequence data from Indian-origin rhesus macaques. The genetic markers used were approximately 18 million SNPs, with marker density 6.93 per kb across the autosomes. We report that the genome-wide recombination rate in rhesus macaques is significantly lower than rates observed in apes or humans, while the distribution of recombination across the macaque genome is more uniform. These observations provide new comparative information regarding the evolution of recombination in primates.


Assuntos
Evolução Molecular , Macaca mulatta/genética , Meiose/genética , Recombinação Genética , Animais , Mapeamento Cromossômico , Marcadores Genéticos , Variação Genética , Genoma , Humanos , Polimorfismo de Nucleotídeo Único , Especificidade da Espécie , Sequenciamento Completo do Genoma
11.
PLoS Biol ; 18(8): e3000817, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813728

RESUMO

During meiosis, chromosomes adopt a specialized organization involving assembly of a cohesin-based axis along their lengths, with DNA loops emanating from this axis. We applied novel, quantitative, and widely applicable cytogenetic strategies to elucidate the molecular bases of this organization using Caenorhabditis elegans. Analyses of wild-type (WT) chromosomes and de novo circular minichromosomes revealed that meiosis-specific HORMA-domain proteins assemble into cohorts in defined numbers and co-organize the axis together with 2 functionally distinct cohesin complexes (REC-8 and COH-3/4) in defined stoichiometry. We further found that REC-8 cohesins, which load during S phase and mediate sister-chromatid cohesion, usually occur as individual complexes, supporting a model wherein sister cohesion is mediated locally by a single cohesin ring. REC-8 complexes are interspersed in an alternating pattern with cohorts of axis-organizing COH-3/4 complexes (averaging 3 per cohort), which are insufficient to confer cohesion but can bind to individual chromatids, suggesting a mechanism to enable formation of asymmetric sister-chromatid loops. Indeed, immunofluorescence/fluorescence in situ hybridization (immuno-FISH) assays demonstrate frequent asymmetry in genomic content between the loops formed on sister chromatids. We discuss how features of chromosome axis/loop architecture inferred from our data can help to explain enigmatic, yet essential, aspects of the meiotic program.


Assuntos
Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Cromátides/ultraestrutura , Proteínas Cromossômicas não Histona/genética , Cromossomos/ultraestrutura , Meiose , Complexo Sinaptonêmico/ultraestrutura , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/metabolismo , Cromátides/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Segregação de Cromossomos , Cromossomos/metabolismo , Análise Citogenética , Hibridização in Situ Fluorescente , Fase S/genética , Complexo Sinaptonêmico/metabolismo
12.
Nat Commun ; 11(1): 4345, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859945

RESUMO

Chromosome movements and programmed DNA double-strand breaks (DSBs) promote homologue pairing and initiate recombination at meiosis onset. Meiotic progression involves checkpoint-controlled termination of these events when all homologue pairs achieve synapsis and form crossover precursors. Exploiting the temporo-spatial organisation of the C. elegans germline and time-resolved methods of protein removal, we show that surveillance of the synaptonemal complex (SC) controls meiotic progression. In nuclei with fully synapsed homologues and crossover precursors, removing different meiosis-specific cohesin complexes, which are individually required for SC stability, or a SC central region component causes functional redeployment of the chromosome movement and DSB machinery, triggering whole-nucleus reorganisation. This apparent reversal of the meiotic programme requires CHK-2 kinase reactivation via signalling from chromosome axes containing HORMA proteins, but occurs in the absence of transcriptional changes. Our results uncover an unexpected plasticity of the meiotic programme and show how chromosome signalling orchestrates nuclear organisation and meiotic progression.


Assuntos
Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Estruturas Cromossômicas/metabolismo , Meiose/fisiologia , Animais , Proteínas de Caenorhabditis elegans/metabolismo , Pontos de Checagem do Ciclo Celular , Quinase do Ponto de Checagem 2/metabolismo , Pareamento Cromossômico , Quebras de DNA de Cadeia Dupla , Complexo Sinaptonêmico/metabolismo
13.
Sheng Li Xue Bao ; 72(4): 513-522, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32820314

RESUMO

Mammalian oocytes within Graafian follicles are arrested at prophase I of meiosis. C-type natriuretic peptide (NPPC), secreted by mural granulosa cells (MGCs), maintains oocyte meiotic arrest via binding to its cognate receptor natriuretic peptide receptor 2 (NPR2) and producing cyclic guanosine monophosphate (cGMP). NPR2 is most concentrated in the cumulus cells. In addition, cAMP, gap junction, inosine monophosphate dehydrogenase (IMPDH) and other important regulatory factors are also involved in meiotic arrest. Luteinizing hormone (LH) then rapidly decreases cGMP and induces oocyte meiotic resumption. In this paper, advances in the molecular mechanisms of meiotic arrest and LH-induced meiotic resumption were reviewed. This paper may provide new ideas for the prevention, diagnosis and treatment of related reproductive diseases.


Assuntos
Hormônio Luteinizante , Oócitos , Animais , Células do Cúmulo , Feminino , Meiose , Peptídeo Natriurético Tipo C/genética
14.
Mol Cell ; 80(1): 9-20, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860741

RESUMO

Cell division requires the assembly and organization of a microtubule spindle for the proper separation of chromosomes in mitosis and meiosis. Phase separation is an emerging paradigm for understanding spatial and temporal regulation of a variety of cellular processes, including cell division. Phase-separated condensates have been recently discovered at many structures during cell division as a possible mechanism for properly localizing, organizing, and activating proteins involved in cell division. Here, we review how these condensates play roles in regulating microtubule density and organization and spindle assembly and function and in activating some of the key players in cell division. We conclude with perspectives on areas of future research for this exciting and rapidly advancing field.


Assuntos
Divisão Celular , Animais , Cromossomos/metabolismo , Humanos , Meiose , Microtúbulos/metabolismo , Fuso Acromático/metabolismo
15.
Am J Hum Genet ; 107(2): 342-351, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32673564

RESUMO

Male infertility affects ∼7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity.


Assuntos
Pontos de Checagem do Ciclo Celular/genética , Infertilidade Masculina/genética , Meiose/genética , Mutação/genética , Proteínas/genética , Espermatogênese/genética , Adulto , Alelos , Animais , Azoospermia/genética , Homozigoto , Humanos , Masculino , Camundongos , Fenótipo , Espermatozoides/anormalidades , Testículo/anormalidades , Turquia , Sequenciamento Completo do Exoma/métodos
16.
J Biosci Bioeng ; 130(4): 367-373, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32646632

RESUMO

Cross hybridization breeding of sake yeasts is hampered by difficulty in acquisition of haploid cells through sporulation. We previously demonstrated that typical sake yeast strains were defective in meiotic chromosome recombination, which caused poor sporulation and loss of spore viability. In this study, we screened a single copy plasmid genomic DNA library of the laboratory Saccharomyces cerevisiae GRF88 for genes that might complement the meiotic recombination defect of UTCAH-3, a strain derived from the sake yeast Kyokai no. 7 (K7). We identified the SPO11 gene of the laboratory strain (ScSPO11), encoding a meiosis-specific endonuclease that catalyzes DNA double-strand breaks required for meiotic recombination, as a gene that restored meiotic recombination and spore viability of UTCAH-3. K7SPO11 could not restore sporulation efficiency and spore viability of UTCAH-3 and a laboratory strain BY4743 spo11Δ/spo11Δ, indicating that K7SPO11 is not functional. Sequence analysis of the SPO11 genes of various Kyokai sake yeasts (K1, and K3-K10) revealed that the K7 group of sake yeasts (K6, K7, K9, and K10) had a mutual missense mutation (C73T) in addition to other three common mutations present in all Kyokai yeasts tested. ScSPO11C73T created through in vitro mutagenesis could not restore spore viability of BY4743 spo11Δ/spo11Δ. On the other hand, K8SPO11, which have the three common mutations except for C73T could restore spore viability of BY4743 spo11Δ/spo11Δ. These results suggest that C73T might be a causative mutation of recombination defect in K7SPO11. Moreover, we found that the introduction of ScRIM15 restored sporulation efficiency but not spore viability.


Assuntos
Bebidas Alcoólicas/microbiologia , Endodesoxirribonucleases/genética , Meiose/genética , Recombinação Genética/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Clonagem Molecular , Quebras de DNA de Cadeia Dupla , Mutação , Saccharomyces cerevisiae/citologia
17.
Gene ; 757: 144929, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32622990

RESUMO

Phaeodactylum tricornutum is a model microalgae that is widely used to study diatom physiology and ecology. Since the meiotic process and sexual cycle have never been observed directly, P. tricornutum has been considered to be an asexual species. However, phylogenetic analysis of the P. tricornutum genome has revealed a series of meiosis-specific gene homologues in this species. We identified two copies of differently transcribed SPO11 homologs that contain the conserved motifs of Winged-helix and Toprim domains. The homolog PtSPO11-3 interacts with TopoVIB in yeast two-hybrid analysis, whereas the homolog PtSPO11-2 could rescue the sporulation defect of a Spo11 yeast mutant strain. PtSPO11-2 was also found to be significantly up-regulated at low temperatures in P. tricornutum and its key catalytic residue was important to the homolog's function in sporulation. The results herein provide positive clue that meiosis and sexual reproduction could exist in this diatom.


Assuntos
Domínio Catalítico , Diatomáceas/genética , Endodesoxirribonucleases/metabolismo , Meiose , Microalgas/genética , Sequência Conservada , Diatomáceas/fisiologia , Endodesoxirribonucleases/química , Endodesoxirribonucleases/genética , Microalgas/fisiologia , Ligação Proteica , Multimerização Proteica
18.
Gene ; 758: 144966, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32687945

RESUMO

RAD21 (also known as KIAA0078, NXP1, HR21, Mcd1, Scc1, and hereafter called RAD21), an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans. RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1a, SMC3, and SCC3 [STAG1 (SA1) and STAG2 (SA2) in metazoans] proteins, involved in sister chromatid cohesion. This function is essential for proper chromosome segregation, post-replicative DNA repair, and prevention of inappropriate recombination between repetitive regions. In interphase, cohesin also functions in the control of gene expression by binding to numerous sites within the genome. In addition to playing roles in the normal cell cycle and DNA DSB repair, RAD21 is also linked to the apoptotic pathways. Germline heterozygous or homozygous missense mutations in RAD21 have been associated with human genetic disorders, including developmental diseases such as Cornelia de Lange syndrome (CdLS) and chronic intestinal pseudo-obstruction (CIPO) called Mungan syndrome, respectively, and collectively termed as cohesinopathies. Somatic mutations and amplification of the RAD21 have also been widely reported in both human solid and hematopoietic tumors. Considering the role of RAD21 in a broad range of cellular processes that are hot spots in neoplasm, it is not surprising that the deregulation of RAD21 has been increasingly evident in human cancers. Herein, we review the biology of RAD21 and the cellular processes that this important protein regulates and discuss the significance of RAD21 deregulation in cancer and cohesinopathies.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Neoplasias/genética , Apoptose/genética , Esôfago de Barrett/genética , Quebras de DNA de Cadeia Dupla , Síndrome de Cornélia de Lange/genética , Hematopoese/genética , Humanos , Pseudo-Obstrução Intestinal/genética , Meiose/genética , Neoplasias/patologia
19.
PLoS Genet ; 16(7): e1008918, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730246

RESUMO

Holocentric chromosomes possess multiple kinetochores along their length rather than the single centromere typical of other chromosomes [1]. They have been described for the first time in cytogenetic experiments dating from 1935 and, since this first observation, the term holocentric chromosome has referred to chromosomes that: i. lack the primary constriction corresponding to centromere observed in monocentric chromosomes [2]; ii. possess multiple kinetochores dispersed along the chromosomal axis so that microtubules bind to chromosomes along their entire length and move broadside to the pole from the metaphase plate [3]. These chromosomes are also termed holokinetic, because, during cell division, chromatids move apart in parallel and do not form the classical V-shaped figures typical of monocentric chromosomes [4-6]. Holocentric chromosomes evolved several times during both animal and plant evolution and are currently reported in about eight hundred diverse species, including plants, insects, arachnids and nematodes [7,8]. As a consequence of their diffuse kinetochores, holocentric chromosomes may stabilize chromosomal fragments favouring karyotype rearrangements [9,10]. However, holocentric chromosome may also present limitations to crossing over causing a restriction of the number of chiasma in bivalents [11] and may cause a restructuring of meiotic divisions resulting in an inverted meiosis [12].


Assuntos
Caenorhabditis elegans/genética , Cromossomos/genética , Cinetocoros/ultraestrutura , Meiose/genética , Animais , Caenorhabditis elegans/citologia , Centrômero/genética , Centrômero/ultraestrutura , Cromátides/genética , Cromátides/ultraestrutura , Segregação de Cromossomos/genética , Cromossomos/ultraestrutura , Cariótipo , Plantas/genética
20.
PLoS Genet ; 16(7): e1008904, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730253

RESUMO

The conserved ATPase, PCH-2/TRIP13, is required during both the spindle checkpoint and meiotic prophase. However, its specific role in regulating meiotic homolog pairing, synapsis and recombination has been enigmatic. Here, we report that this enzyme is required to proofread meiotic homolog interactions. We generated a mutant version of PCH-2 in C. elegans that binds ATP but cannot hydrolyze it: pch-2E253Q. In vitro, this mutant can bind a known substrate but is unable to remodel it. This mutation results in some non-homologous synapsis and impaired crossover assurance. Surprisingly, worms with a null mutation in PCH-2's adapter protein, CMT-1, the ortholog of p31comet, localize PCH-2 to meiotic chromosomes, exhibit non-homologous synapsis and lose crossover assurance. The similarity in phenotypes between cmt-1 and pch-2E253Q mutants suggest that PCH-2 can bind its meiotic substrates in the absence of CMT-1, in contrast to its role during the spindle checkpoint, but requires its adapter to hydrolyze ATP and remodel them.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Meiose/genética , Proteínas Nucleares/genética , Adenosina Trifosfatases/genética , Trifosfato de Adenosina/genética , Animais , Caenorhabditis elegans/genética , Pareamento Cromossômico/genética , Segregação de Cromossomos/genética , Cromossomos/genética , Humanos , Mutação/genética , Fuso Acromático/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA