GO:0045835 negative regulation of meiotic nuclear division: Checkpoint Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0045835 (negative regulation of meiotic nuclear division) describes any process that stops, prevents, or reduces the frequency, rate or extent of meiosis.
• Negative regulation of meiosis is essential for preventing inappropriate meiotic entry, limiting recombination to one round per cell cycle, and protecting genome integrity.
• Key negative regulators include the nuclear poly(A)-binding protein Pab2 in fission yeast, the Mek1 kinase in budding yeast, and the FIGNL1-FIRRM complex in mammals.
• DMC1 and RAD51 are positively regulated in most contexts, but DMC1 can attenuate RAD51-mediated recombination, illustrating context-dependent negative control.
• Dysregulation of meiotic negative regulators such as HORMAD1 is linked to tumour-specific mitotic perturbations and sensitivity to mitotic kinase inhibitors.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable precise dissection of negative regulatory circuits in meiosis.
Description
Meiosis is a specialized cell division that halves the chromosome number to produce haploid gametes, and its proper execution is critical for sexual reproduction and genome stability. Because meiosis is energetically costly and potentially mutagenic if misregulated, cells have evolved robust negative regulatory mechanisms that prevent inappropriate meiotic entry, limit recombination to a single round per cell cycle, and coordinate meiotic progression with developmental cues. The Gene Ontology term GO:0045835, negative regulation of meiotic nuclear division, captures these inhibitory processes that stop, prevent, or reduce the frequency, rate or extent of meiosis. Research into negative regulation of meiosis has revealed diverse molecular players, from RNA-binding proteins that control meiotic gene expression to kinases that phosphorylate recombination factors and structural proteins that modulate chromosome dynamics. In the fission yeast Schizosaccharomyces pombe, the nuclear poly(A)-binding protein Pab2 negatively regulates meiotic gene expression, ensuring that meiosis occurs only under appropriate conditions. In budding yeast, the Mek1 kinase phosphorylates Rad54 to regulate meiotic recombination, acting as a negative regulator of interhomolog recombination. In mammals, the FIGNL1-FIRRM complex is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading, highlighting a conserved theme of negative control over recombinase activity. Understanding negative regulation of meiotic nuclear division is important for reproductive biology, cancer research, and evolutionary studies. Dysregulation of meiotic negative regulators can lead to aneuploidy, infertility, and cancer. For example, tumour-specific expression of HORMAD1, a meiosis-specific protein, perturbs mitotic arrest and drives sensitivity to mitotic kinase inhibitors, linking meiotic regulation to cancer therapy. This article synthesizes authoritative QuickGO data and verified PubMed literature to provide a research-grade overview of GO:0045835, its mechanisms, key genes, and experimental approaches.
negative regulation of meiotic nuclear division At A Glance
| GO ID | GO:0045835 |
|---|---|
| GO term | negative regulation of meiotic nuclear division |
| Ontology | biological_process |
| Synonym | down regulation of meiosis, down-regulation of meiosis, downregulation of meiosis, inhibition of meiosis, negative regulation of meiosis |
| Major function | Stops, prevents, or reduces the frequency, rate or extent of meiosis |
| Related processes | Meiotic cell cycle, homologous recombination, checkpoint control |
| Key regulators | Pab2, Mek1, FIGNL1-FIRRM, DMC1, RAD51, HORMAD1 |
| Organisms studied | Schizosaccharomyces pombe, Saccharomyces cerevisiae, Arabidopsis thaliana, mammals, Candida glabrata |
What Is GO:0045835?
GO:0045835, negative regulation of meiotic nuclear division, is defined as any process that stops, prevents, or reduces the frequency, rate or extent of meiosis. This biological process encompasses molecular mechanisms that inhibit the initiation, progression, or completion of meiotic nuclear division, including transcriptional repression of meiotic genes, post-translational modification of recombination machinery, and checkpoint-mediated arrest. It is distinct from positive regulation of meiosis and is essential for coordinating meiotic entry with nutrient availability, developmental signals, and genome integrity checkpoints.
Why Is negative regulation of meiotic nuclear division Important in Cell Biology?
Negative regulation of meiotic nuclear division is fundamental to reproductive success and genome stability because it ensures that meiosis occurs only under favorable conditions and that recombination is tightly controlled. Defects in negative regulatory pathways can lead to inappropriate meiotic entry, excessive or mislocalized recombination, aneuploidy, and infertility. Moreover, meiotic regulators are frequently misexpressed in cancer, where they can perturb mitotic division and create therapeutic vulnerabilities. Understanding these inhibitory mechanisms therefore has broad implications for developmental biology, reproductive medicine, and oncology.
• Prevents inappropriate meiotic entry under unfavorable conditions, conserving cellular resources.
• Limits recombination to one round per cell cycle, avoiding genome instability.
• Coordinates meiotic progression with developmental and nutritional cues.
• Dysregulation leads to aneuploidy and infertility in mammals.
• Meiotic negative regulators such as HORMAD1 are misexpressed in tumours and affect mitotic arrest.
• Provides targets for contraceptives and fertility treatments.
• Informs cancer therapy by exploiting meiotic gene dependencies.
• Conserved from yeast to humans, enabling model organism studies.
• Essential for understanding evolutionary adaptation of reproductive strategies.
• Guides CRISPR-based functional genomics in meiosis research.
What Happens During negative regulation of meiotic nuclear division?
Transcriptional and post-transcriptional repression of meiotic genes
In simple terms: Cells can stop meiosis by turning off or degrading the RNA messages needed for meiosis.
Negative regulation of meiotic nuclear division often begins with transcriptional and post-transcriptional control of meiotic gene expression. In fission yeast, the nuclear poly(A)-binding protein Pab2 negatively regulates meiotic gene expression, likely by promoting RNA degradation or preventing efficient translation of meiotic transcripts. This ensures that meiosis is not initiated unless conditions are appropriate. Similarly, in the human fungal pathogen Candida glabrata, regulation of meiotic gene expression is functional, indicating conserved mechanisms of meiotic gene repression. These RNA-level controls provide a rapid and reversible way to inhibit meiosis.
Checkpoint-mediated inhibition of meiotic progression
In simple terms: Quality-control checkpoints can pause or stop meiosis if something goes wrong.
Meiotic cells possess checkpoints that monitor chromosome pairing, recombination, and synapsis, and can halt meiotic nuclear division when defects are detected. In budding yeast, the Mek1 kinase is a key effector of the meiotic recombination checkpoint; it phosphorylates Rad54 to downregulate its activity and prevent inappropriate interhomolog recombination. This negative regulation ensures that recombination intermediates are resolved correctly before meiotic divisions proceed. Checkpoint-mediated inhibition is critical for preventing chromosome missegregation and aneuploidy.
Negative control of recombinase loading and activity
In simple terms: Cells use specific proteins to stop recombinases from loading onto DNA at the wrong time or place.
The loading of RAD51 and DMC1 recombinases onto DNA is tightly controlled, and negative regulators prevent their inappropriate accumulation. The FIGNL1-FIRRM complex is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading in mammals. In Arabidopsis, DMC1 attenuates RAD51-mediated recombination, acting as a negative regulator of RAD51 activity. These mechanisms ensure that recombination occurs only at the right time and place, protecting genome integrity.
Regulation of meiotic maturation in oocytes
In simple terms: In eggs, meiosis is paused and only resumes when the time is right, controlled by external signals and the cytoskeleton.
In mammalian oocytes, meiotic maturation is regulated by an interplay between exogenous cues and the microtubule cytoskeleton. Negative regulation keeps the oocyte arrested at specific stages until hormonal signals trigger resumption. This control is essential for proper chromosome segregation and prevents premature or delayed meiosis, which can lead to infertility or birth defects.
Tumour-specific perturbation of meiotic regulators
In simple terms: Cancer cells sometimes turn on meiosis genes, which messes up their normal division and can be exploited for therapy.
Tumour-specific expression of the meiosis-specific protein HORMAD1 perturbs mitotic arrest and drives sensitivity to mitotic kinase inhibitors. This illustrates how negative regulators of meiosis, when misexpressed in mitotic cells, can disrupt cell cycle checkpoints and create therapeutic vulnerabilities. Understanding these interactions links meiotic negative regulation to cancer biology and drug development.
Key Genes Involved in GO:0045835 negative regulation of meiotic nuclear division
The following genes and proteins are experimentally validated participants in negative regulation of meiotic nuclear division, based on the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| Pab2 | Nuclear poly(A)-binding protein that negatively regulates meiotic gene expression in fission yeast | RNA-level control of meiotic entry |
| Mek1 | Kinase that phosphorylates Rad54 to inhibit interhomolog recombination in budding yeast | Checkpoint-mediated negative regulation |
| Rad54 | Recombination factor whose activity is downregulated by Mek1 phosphorylation | Target of negative regulation |
| FIGNL1 | Component of FIGNL1-FIRRM complex that prevents inappropriate RAD51/DMC1 loading | Essential for meiotic recombination |
| FIRRM | Partner of FIGNL1 in complex that regulates recombinase loading | Negative control of RAD51/DMC1 |
| RAD51 | Recombinase whose loading is negatively regulated by FIGNL1-FIRRM | Central to homologous recombination |
| DMC1 | Meiosis-specific recombinase that can attenuate RAD51-mediated recombination | Context-dependent negative regulator |
| HORMAD1 | Meiosis-specific protein whose tumour-specific expression perturbs mitotic arrest | Link to cancer and mitotic kinase inhibitors |
| Candida glabrata meiotic regulators | Functional meiotic gene expression regulation in fungal pathogen | Conserved negative regulation |
| Oocyte maturation regulators | Proteins integrating exogenous cues and microtubule cytoskeleton | Control of meiotic arrest/resumption |
| RAD51/DMC1 regulators | Positive and negative regulators of recombinases | Broad control of homologous recombination |
| Meiotic checkpoint kinases | Kinases that halt meiosis upon defects | Quality control |
| Transcription factors for meiotic genes | Repressors of meiotic gene transcription | Transcriptional negative regulation |
| RNA-binding proteins | Post-transcriptional repression of meiotic transcripts | RNA-level control |
| Microtubule-associated proteins | Mediate oocyte meiotic spindle dynamics | Oocyte maturation control |
| FIGNL1-FIRRM complex components | Prevent DNA damage-independent recombinase loading | Genome stability |
| HORMAD1-interacting proteins | Modulate mitotic arrest in cancer cells | Cancer therapy target |
How Is negative regulation of meiotic nuclear division Regulated?
Negative regulation of meiotic nuclear division is itself subject to multiple layers of control. In fission yeast, Pab2-mediated RNA regulation responds to nutritional and environmental cues. In budding yeast, the Mek1 checkpoint kinase is activated by recombination defects and phosphorylates Rad54 to inhibit recombination. In mammals, the FIGNL1-FIRRM complex is regulated during meiotic prophase to prevent premature recombinase loading. Additionally, oocyte meiotic maturation is controlled by hormonal signals and the microtubule cytoskeleton. In cancer cells, HORMAD1 expression is tumour-specific and perturbs mitotic arrest, suggesting that meiotic regulators can be co-opted by oncogenic pathways. These regulatory inputs ensure that meiosis is inhibited unless conditions are appropriate.
negative regulation of meiotic nuclear division and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HORMAD1 | Cancer, mitotic arrest perturbation | Cancer cell lines with HORMAD1 overexpression or knockout |
| FIGNL1 | Meiotic recombination defects, genome instability | Mouse knockout models, human cell lines |
| DMC1 | Infertility, recombination disorders | Arabidopsis dmc1 mutants, mammalian knockout mice |
| RAD51 | Cancer predisposition, genome instability | CRISPR knockout in cancer cell lines |
| Mek1 | Meiotic checkpoint defects (yeast model) | Saccharomyces cerevisiae mek1 mutants |
Infertility and aneuploidy
Proper negative regulation of meiotic nuclear division is essential for accurate chromosome segregation. Defects in meiotic checkpoints or recombinase control can lead to aneuploidy, miscarriage, and infertility. For example, misregulation of oocyte maturation can result in premature or delayed meiosis, increasing the risk of chromosomal abnormalities.
Cancer
Meiotic genes are frequently misexpressed in tumours. Tumour-specific expression of HORMAD1 perturbs mitotic arrest and drives sensitivity to mitotic kinase inhibitors, suggesting that meiotic negative regulators can be exploited as cancer therapeutic targets. Understanding how meiotic regulatory circuits are rewired in cancer may reveal new treatment strategies.
Fungal pathogenesis
In the human fungal pathogen Candida glabrata, regulation of meiotic gene expression is functional, and this may contribute to its ability to survive and infect hosts. Negative regulation of meiosis in fungal pathogens could be a target for antifungal drug development.
From negative regulation of meiotic nuclear division-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a candidate negative regulator cause premature meiotic entry? | CRISPR knockout in fission yeast or mouse germ cells |
| Does a specific phosphorylation site on Rad54 mediate Mek1-dependent inhibition? | Point mutation knock-in of Rad54 phospho-null or phospho-mimetic alleles in budding yeast |
| Does overexpression of HORMAD1 perturb mitotic arrest in cancer cells? | Overexpression of HORMAD1 in human cancer cell lines |
| Does FIGNL1-FIRRM complex prevent inappropriate RAD51 loading? | Knockout of FIGNL1 or FIRRM in mouse models or human cells |
| Does DMC1 attenuate RAD51-mediated recombination? | DMC1 overexpression or knockout in Arabidopsis |
| Does Pab2 regulate meiotic gene expression at the RNA level? | Tagged knock-in of Pab2 for RNA immunoprecipitation in S. pombe |
How to Study the negative regulation of meiotic nuclear division Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcript levels of meiotic genes | Assess Pab2-mediated repression |
| Phosphoproteomics | Phosphorylation sites on target proteins | Identify Mek1 substrates like Rad54 |
| Fluorescence microscopy | RAD51/DMC1 foci, chromosome synapsis | Visualize recombinase loading |
| CRISPR knockout screening | Gene requirements for meiotic inhibition | Discover novel negative regulators |
| Live-cell imaging | Oocyte meiotic spindle dynamics | Study oocyte maturation |
| ChIP-seq | Chromatin binding of meiotic regulators | Map HORMAD1 binding in cancer cells |
| Yeast genetics | Meiotic progression and spore viability | Test Mek1 pathway mutants |
Transcriptomics and RNA-level analysis
RNA-seq and related methods can quantify meiotic gene expression changes upon perturbation of negative regulators such as Pab2. In Candida glabrata, RNA-seq has been used to assess meiotic gene expression regulation. These approaches reveal transcriptional and post-transcriptional effects.
Proteomics and phosphoproteomics
Mass spectrometry-based proteomics can identify phosphorylation events mediated by kinases like Mek1, including Rad54 phosphorylation. Phosphoproteomics is useful for mapping signaling pathways that inhibit meiosis.
Imaging and cytology
Fluorescence microscopy can visualize recombinase loading (RAD51/DMC1 foci), chromosome synapsis, and meiotic progression in cells with altered negative regulators. Live-cell imaging of oocyte maturation can track meiotic spindle dynamics.
Genetic screens and CRISPR libraries
CRISPR knockout library screening can identify novel negative regulators of meiosis by selecting for cells that undergo inappropriate meiotic entry or recombination. This unbiased approach complements candidate-based studies.
How CRISPR Can Be Used to Study GO:0045835 negative regulation of meiotic nuclear division
Knockout
CRISPR knockout of candidate negative regulators such as FIGNL1, FIRRM, or Pab2 can reveal their essential roles in preventing inappropriate meiotic entry or recombinase loading. Knockout models in yeast, mouse, and human cells enable functional dissection of these pathways.
Point Mutation
Point mutation knock-in can be used to test the function of specific phosphorylation sites, such as Rad54 residues targeted by Mek1. Phospho-null or phospho-mimetic alleles clarify the importance of individual modifications in negative regulation.
Knock-in
Tagged knock-in of genes like Pab2 or HORMAD1 allows for localization, interaction, and RNA-binding studies using epitope tags or fluorescent proteins. This approach preserves endogenous regulation while enabling biochemical analysis.
Overexpression
Overexpression of negative regulators such as HORMAD1 in cancer cells can model tumour-specific misexpression and test sensitivity to mitotic kinase inhibitors. Overexpression of DMC1 in Arabidopsis can attenuate RAD51-mediated recombination, demonstrating negative regulatory capacity.
How EDITGENE Supports negative regulation of meiotic nuclear division Research
Researchers studying negative regulation of meiotic nuclear division-related genes often need to determine whether a candidate gene is causally involved in inhibiting meiosis, and CRISPR-based models provide the most direct way to test this. EDITGENE offers a comprehensive suite of services to accelerate such studies.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of meiotic nuclear division research.
Frequently Asked Questions About negative regulation of meiotic nuclear division
What is GO:0045835?
GO:0045835 is the Gene Ontology term for negative regulation of meiotic nuclear division, defined as any process that stops, prevents, or reduces the frequency, rate or extent of meiosis.
What genes are involved in negative regulation of meiosis?
Key genes include Pab2, Mek1, Rad54, FIGNL1, FIRRM, RAD51, DMC1, and HORMAD1, as shown in yeast, plant, and mammalian studies.
How is meiosis negatively regulated?
Meiosis is negatively regulated through transcriptional and post-transcriptional repression of meiotic genes, checkpoint-mediated inhibition of progression, and negative control of recombinase loading.
What is the role of Mek1 in meiosis?
Mek1 is a kinase that phosphorylates Rad54 to inhibit interhomolog recombination, acting as a negative regulator in budding yeast.
How does FIGNL1-FIRRM complex regulate meiosis?
The FIGNL1-FIRRM complex is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading.
Can DMC1 act as a negative regulator?
Yes, in Arabidopsis, DMC1 attenuates RAD51-mediated recombination, demonstrating a negative regulatory role.
What diseases are linked to defective negative regulation of meiosis?
Defects are linked to infertility, aneuploidy, and cancer, with HORMAD1 misexpression affecting mitotic arrest in tumours.
How can CRISPR be used to study negative regulation of meiosis?
CRISPR knockout, point mutation, knock-in, and overexpression models allow functional testing of candidate negative regulators in various organisms.
What model organisms are used to study negative regulation of meiosis?
Common models include Schizosaccharomyces pombe, Saccharomyces cerevisiae, Arabidopsis thaliana, Candida glabrata, and mammalian cells.
What methods are used to study negative regulation of meiotic nuclear division?
Methods include RNA-seq, phosphoproteomics, fluorescence microscopy, CRISPR screens, and yeast genetics.
Conclusion
Negative regulation of meiotic nuclear division (GO:0045835) is a critical biological process that ensures meiosis occurs only under appropriate conditions and that recombination is tightly controlled. Research across yeast, plants, and mammals has identified diverse molecular players, from RNA-binding proteins like Pab2 to kinases like Mek1 and complexes like FIGNL1-FIRRM. Dysregulation of these pathways is linked to infertility, aneuploidy, and cancer, making them important targets for reproductive medicine and oncology. CRISPR-based models, including knockout, point mutation, knock-in, and overexpression, provide powerful tools to dissect these regulatory mechanisms. EDITGENE offers comprehensive services to support such research, from custom cell model generation to library screening and bioinformatics analysis.
References
- 1. St-André O et al.. 2010. Negative regulation of meiotic gene expression by the nuclear poly(a)-binding protein in fission yeast.. J Biol Chem 285(36):27859-68 PMID: 20622014
- 2. Zainu A et al.. 2024. FIGNL1-FIRRM is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading.. Nat Commun 15(1):7015 PMID: 39147779
- 3. Da Ines O et al.. 2022. DMC1 attenuates RAD51-mediated recombination in Arabidopsis.. PLoS Genet 18(8):e1010322 PMID: 36007010
- 4. Albertini DF. 1992. Regulation of meiotic maturation in the mammalian oocyte: interplay between exogenous cues and the microtubule cytoskeleton.. Bioessays 14(2):97-103 PMID: 1575717
- 5. Walker C et al.. 2026. Tumour specific HORMAD1 expression perturbs mitotic arrest and drives sensitivity to mitotic kinase inhibitors.. Nat Commun 17(1) PMID: 41813673
- 6. Klimova N et al.. 2025. Regulation of meiotic gene expression is functional in the human fungal pathogen Candida glabrata.. FEMS Yeast Res 25 PMID: 40175304
- 7. Ito M et al.. 2024. Positive and negative regulators of RAD51/DMC1 in homologous recombination and DNA replication.. DNA Repair (Amst) 134:103613 PMID: 38142595
- 8. Niu H et al.. 2009. Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation.. Mol Cell 36(3):393-404 PMID: 19917248
