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Trends in Genetics : TIG Jul 2023Recombination-independent homologous pairing represents a prominent yet largely enigmatic feature of chromosome biology. As suggested by studies in the fungus Neurospora... (Review)
Review
Recombination-independent homologous pairing represents a prominent yet largely enigmatic feature of chromosome biology. As suggested by studies in the fungus Neurospora crassa, this process may be based on the direct pairing of homologous DNA molecules. Theoretical search for the DNA structures consistent with those genetic results has led to an all-atom model in which the B-DNA conformation of the paired double helices is strongly shifted toward C-DNA. Coincidentally, C-DNA also features a very shallow major groove that could permit initial homologous contacts without atom-atom clashes. The hereby conjectured role of C-DNA in homologous pairing should encourage the efforts to discover its biological functions and may also clarify the mechanism of recombination-independent recognition of DNA homology.
Topics: DNA; Fungi; Nucleic Acid Conformation; Meiosis
PubMed: 36804168
DOI: 10.1016/j.tig.2023.01.008 -
Current Opinion in Genetics &... Aug 2023The germline produces haploid gametes through a specialized cell division called meiosis. In general, homologous chromosomes from each parent segregate randomly to the... (Review)
Review
The germline produces haploid gametes through a specialized cell division called meiosis. In general, homologous chromosomes from each parent segregate randomly to the daughter cells during meiosis, providing parental alleles with an equal chance of transmission. Meiotic drivers are selfish elements who cheat this process to increase their transmission rate. In female meiosis, selfish centromeres and noncentromeric drivers cheat by preferentially segregating to the egg cell. Selfish centromeres cheat in meiosis I (MI), while noncentromeric drivers can cheat in both meiosis I and meiosis II (MII). Here, we highlight recent advances on our understanding of the molecular mechanisms underlying these genetic cheating strategies, especially focusing on mammalian systems, and discuss new models of how noncentromeric selfish drivers can cheat in MII eggs.
Topics: Animals; Female; Centromere; Meiosis; Germ Cells; Alleles; Mammals
PubMed: 37406428
DOI: 10.1016/j.gde.2023.102082 -
Journal of Assisted Reproduction and... Apr 2022Oocyte developmental competence is defined as the capacity of the female gamete to be fertilized and sustain development to the blastocyst stage. Epigenetic... (Review)
Review
Oocyte developmental competence is defined as the capacity of the female gamete to be fertilized and sustain development to the blastocyst stage. Epigenetic reprogramming, a correct cell division pattern, and an efficient DNA damage response are all critical events that, before embryonic genome activation, are governed by maternally inherited factors such as maternal-effect gene (MEG) products. Although these molecules are stored inside the oocyte until ovulation and exert their main role during fertilization and preimplantation development, some of them are already functioning during folliculogenesis and oocyte meiosis resumption. This mini review summarizes the crucial roles played by MEGs during oocyte maturation, fertilization, and preimplantation development with a direct/indirect effect on the acquisition or maintenance of oocyte competence. Our aim is to inspire future research on a topic with potential clinical perspectives for the prediction and treatment of female infertility.
Topics: Blastocyst; Embryonic Development; Female; Humans; Maternal Inheritance; Meiosis; Oocytes; Oogenesis
PubMed: 35165782
DOI: 10.1007/s10815-022-02434-y -
Human Reproduction (Oxford, England) Nov 2023Are variants of genes involved in meiosis initiation responsible for premature ovarian insufficiency (POI)?
STUDY QUESTION
Are variants of genes involved in meiosis initiation responsible for premature ovarian insufficiency (POI)?
SUMMARY ANSWER
A MEIOSIN variant participates in the pathogenesis of human POI by impairing meiosis due to insufficient transcriptional activation of essential meiotic genes.
WHAT IS KNOWN ALREADY
Meiosis is the key event for the establishment of the ovarian reserve, and several gene defects impairing meiotic homologous recombination have been found to contribute to the pathogenesis of POI. Although STRA8 and MEIOISN variants have been found to associate with POI in a recent study, the condition of other meiosis initiation genes is unknown and direct evidence of variants participating in the pathogenesis of POI is still lacking.
STUDY DESIGN, SIZE, DURATION
This was a retrospective genetic study. An in-house whole exome sequencing (WES) database of 1030 idiopathic POI patients was screened for variations of meiosis initiation genes.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Homozygous or compound heterozygous variations of genes involved in meiosis initiation were screened in the in-house WES database. The pathogenicity of the variation was verified by in vitro experiments, including protein structure prediction and dual-luciferase reporter assay. The effect of the variant on ovarian function and meiosis was demonstrated through histological analyses in a point mutation mouse model.
MAIN RESULTS AND THE ROLE OF CHANCE
One homozygous variant in MEIOSIN (c.1735C>T, p.R579W) and one in STRA8 (c.258 + 1G>A), which initiates meiosis via the retinoic acid-dependent pathway, were identified in a patient with idiopathic POI respectively. The STRA8 variation has been reported in the recently published work. For the MEIOSIN variation, the dual-luciferase reporter assay revealed that the variant adversely affected the transcriptional function of MEIOSIN in upregulating meiotic genes. Furthermore, knock-in mice with the homologous mutation confirmed that the variation impacted the meiotic prophase I program and accelerated oocyte depletion. Moreover, the variant p.R579W localizing in the high-mobility group (HMG) box domain disrupted the nuclear localization of the MEIOSIN protein but was dispensable for the cell-cycle switch of oocytes, suggesting a unique role of the MEIOSIN HMG box domain in meiosis initiation.
LIMITATIONS, REASONS FOR CAUTION
Further studies are needed to explore the role of other meiosis initiation genes in the pathogenesis of POI.
WIDER IMPLICATIONS OF THE FINDINGS
The MEIOSIN variant was verified to cause POI by impaired transcriptional regulation of meiotic genes and was inherited by a recessive mode. The function of HMG box domain in MEIOSIN protein was also expanded by this study. Although causative variations in meiotic initiation genes are rare in POI, our study confirmed the pathogenicity of a MEIOSIN variant and elucidated another mechanism of human infertility.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the National Key Research & Developmental Program of China (2022YFC2703800, 2022YFC2703000), National Natural Science Foundation for Distinguished Young Scholars (82125014), National Natural Science Foundation of China (32070847, 32170867, 82071609), Basic Science Center Program of NSFC (31988101), Natural Science Foundation of Shandong Province for Grand Basic Projects (ZR2021ZD33), Natural Science Foundation of Shandong Province for Excellent Young Scholars (ZR2022YQ69), Taishan Scholars Program for Young Experts of Shandong Province (tsqn202211371), and Qilu Young Scholars Program of Shandong University. The authors declare no conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Humans; Animals; Mice; Female; Meiosis; Retrospective Studies; Menopause, Premature; Primary Ovarian Insufficiency; Luciferases
PubMed: 37982418
DOI: 10.1093/humrep/dead084 -
The EMBO Journal Aug 2023Meiotic recombination is initiated by the formation of DNA double-strand breaks (DSBs), essential for fertility and genetic diversity. In the mouse, DSBs are formed by...
Meiotic recombination is initiated by the formation of DNA double-strand breaks (DSBs), essential for fertility and genetic diversity. In the mouse, DSBs are formed by the catalytic TOPOVIL complex consisting of SPO11 and TOPOVIBL. To preserve genome integrity, the activity of the TOPOVIL complex is finely controlled by several meiotic factors including REC114, MEI4, and IHO1, but the underlying mechanism is poorly understood. Here, we report that mouse REC114 forms homodimers, that it associates with MEI4 as a 2:1 heterotrimer that further dimerizes, and that IHO1 forms coiled-coil-based tetramers. Using AlphaFold2 modeling combined with biochemical characterization, we uncovered the molecular details of these assemblies. Finally, we show that IHO1 directly interacts with the PH domain of REC114 by recognizing the same surface as TOPOVIBL and another meiotic factor ANKRD31. These results provide strong evidence for the existence of a ternary IHO1-REC114-MEI4 complex and suggest that REC114 could act as a potential regulatory platform mediating mutually exclusive interactions with several partners.
Topics: Animals; Mice; Cell Cycle Proteins; DNA; Homologous Recombination; Meiosis
PubMed: 37431931
DOI: 10.15252/embj.2023113866 -
MicrobiologyOpen Jun 2022The fission yeast Schizosaccharomyces pombe employs two main strategies to adapt to the environment and survive when starved for nutrients. The strategies employ... (Review)
Review
The fission yeast Schizosaccharomyces pombe employs two main strategies to adapt to the environment and survive when starved for nutrients. The strategies employ sporulation via sexual differentiation and extension of the chronological lifespan. When a cell is exposed to nutrient starvation in the presence of a cell of the opposite sex, the cells undergo fusion through conjugation and sporulation through meiosis. S. pombe spores are highly resistant to diverse stresses and may survive for a very long time. In this minireview, among the various sexual differentiation processes induced by starvation, we focused on and summarized the findings of the molecular mechanisms of spore formation in fission yeast. Furthermore, comparative measurements of the chronological lifespan of stationary phase cells and G cells and the survival period of spore cells revealed that the spore cells survived for a long period, indicating the presence of an effective mechanism for survival. Currently, many molecules involved in sporulation and their functions are being discovered; however, our understanding of these is not complete. Further understanding of spores may not only deepen our comprehension of sexual differentiation but may also provide hints for sustaining life.
Topics: Meiosis; Schizosaccharomyces; Spores, Fungal
PubMed: 35765188
DOI: 10.1002/mbo3.1303 -
Asian Journal of Andrology 2021Male meiosis is a complex process whereby spermatocytes undergo cell division to form haploid cells. This review focuses on the role of retinoic acid (RA) in meiosis, as... (Review)
Review
Male meiosis is a complex process whereby spermatocytes undergo cell division to form haploid cells. This review focuses on the role of retinoic acid (RA) in meiosis, as well as several processes regulated by RA before cell entry into meiosis that are critical for proper meiotic entry and completion. Here, we discuss RA metabolism in the testis as well as the roles of stimulated by retinoic acid gene 8 (STRA8) and MEIOSIN, which are responsive to RA and are critical for meiosis. We assert that transcriptional regulation in the spermatogonia is critical for successful meiosis.
Topics: Animals; Cell Differentiation; Humans; Meiosis; Spermatogenesis; Tretinoin
PubMed: 34472453
DOI: 10.4103/aja202156 -
Current Opinion in Genetics &... Oct 2023Female meiosis is fundamentally asymmetric, creating an arena for genetic elements to compete for inclusion in the egg to maximize their transmission. Centromeres, as... (Review)
Review
Female meiosis is fundamentally asymmetric, creating an arena for genetic elements to compete for inclusion in the egg to maximize their transmission. Centromeres, as mediators of chromosomal segregation, are prime candidates to evolve via 'female meiotic drive'. According to the centromere-drive model, the asymmetry of female meiosis ignites a coevolutionary arms race between selfish centromeres and kinetochore proteins, the by-product of which is accelerated sequence divergence. Here, I describe and compare plant models that have been instrumental in uncovering the mechanistic basis of female meiotic drive (maize) and the dynamics of active selfish centromeres in nature (monkeyflowers). Then, I speculate on the mechanistic basis of drive in monkeyflowers, discuss how centromere strength influences chromosomal segregation in plants, and describe new insights into the evolution of plant centromeres.
Topics: Centromere; Chromosome Segregation; Meiosis
PubMed: 37633231
DOI: 10.1016/j.gde.2023.102101 -
Sheng Li Xue Bao : [Acta Physiologica... Feb 2020Meiosis is a special type of cell division to produce haploid gametes with intact genome. The behavior of homologous chromosomes during the first division (meiosis... (Review)
Review
Meiosis is a special type of cell division to produce haploid gametes with intact genome. The behavior of homologous chromosomes during the first division (meiosis prophase I) is the most prominent feature of meiosis. During meiosis prophase I, synaptonemal complex (SC) formed between homologous chromosomes to promote the initiation and repair of programmed DNA double-strand breaks (DSBs), which is necessary for the correct recognition, pairing, recombination and separation of homologous chromosomes. In this paper, we reviewed the recent research progress on the composition and function of SC, discussed how the assembly of SC affected the repair of DSBs, and also summarized the known mutations on SC genes which were responsible for human reproductive disorders. On this basis, we also explored the future research direction of this field.
Topics: DNA Breaks, Double-Stranded; DNA Repair; Humans; Meiotic Prophase I; Synaptonemal Complex
PubMed: 32099986
DOI: No ID Found -
Plant Science : An International... Oct 2022In triploid watermelon (Citrullus lanatus), the homologous chromosomes of germ cells are disorder during meiosis, resulting in the failure of seeds formation and...
In triploid watermelon (Citrullus lanatus), the homologous chromosomes of germ cells are disorder during meiosis, resulting in the failure of seeds formation and producing seedless fruit. Therefore, mutating the genes specifically functioning in meiosis may be an alternative way to achieve seedless watermelon. REC8, as a key component of the cohesin complex in meiosis, is dramatically essential for sister chromatid cohesion and chromosome segregation. However, the role of REC8 in meiosis has not yet been characterized in watermelon. Here, we identified ClREC8 as a member of RAD21/REC8 family with a high expression in male and female flowers of watermelon. In situ hybridization analysis showed that ClREC8 was highly expressed at the early stage of meiosis during pollen formation. Knocking out ClREC8 in watermelon led to decline of pollen vitality. After pollinating with foreign normal pollen, the ovaries of ClREC8 knockout lines could inflate normally but failed to form seeds. We further compared the meiosis chromosomes of pollen mother cells in different stages between the knockout lines and the corresponding wild type. The results indicated that ClREC8 was required for the monopolar orientation of the sister kinetochores in Meiosis I. Additionally, transcriptome sequencing (RNA-seq) analysis between WT and the knockout lines revealed that the disruption of ClREC8 caused the expression levels of mitosis-related genes and meiosis-related genes to decrease. Our results demonstrated ClREC8 has a specific role in Meiosis I of watermelon germ cells, and loss-of-function of the ClREC8 led to seedless fruit, which may provide an alternative strategy to breed cultivars with seedless watermelon.
Topics: Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Citrullus; Meiosis; Nuclear Proteins; Phosphoproteins; Plant Breeding
PubMed: 35905897
DOI: 10.1016/j.plantsci.2022.111394