GO:0005715 late recombination nodule: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0005715 late recombination nodule is an electron-dense structure associated with meiotic chromosomes during pachytene of meiosis I.
• Late recombination nodules are cytological markers of reciprocal crossover events and are enriched in pro-crossover proteins such as COSA-1 in C. elegans.
• The number and distribution of late recombination nodules correlate with the pattern of synapsis and early recombination nodules in plants such as maize.
• Late recombination nodules are distinct from early recombination nodules and appear after synapsis is largely complete, marking the transition to crossover maturation.
• CDK2 activity at meiotic crossover sites is required for late recombination nodule formation and crossover completion in mouse spermatocytes.
• Studying late recombination nodules requires a combination of electron microscopy, immunofluorescence, and genetic perturbation of pro-crossover factors.
Description
Late recombination nodules (GO:0005715) are electron-dense structures that form on meiotic chromosomes during pachytene of meiosis I. They are cytologically visible under the electron microscope and are considered the morphological counterpart of reciprocal crossover events, making them a key readout for meiotic recombination. In many organisms, late recombination nodules appear after synapsis is largely complete and are enriched in pro-crossover proteins, including COSA-1 in Caenorhabditis elegans. Because meiotic recombination is essential for faithful chromosome segregation and genetic diversity, understanding the composition and regulation of late recombination nodules has broad implications for reproductive biology, plant breeding, and cancer research. This article summarizes the current knowledge of late recombination nodule structure, assembly, molecular regulation, and the experimental methods used to study it, based on published literature.
late recombination nodule At A Glance
| GO ID | GO:0005715 |
|---|---|
| GO term | late recombination nodule |
| Ontology | cellular_component |
| Synonym | none |
| Definition | An electron dense structure that is associated with meiotic chromosomes in pachytene during meiosis I. |
| Major function | Cytological marker of reciprocal crossover events during meiosis I. |
| Associated proteins | COSA-1 in C. elegans; CDK2 in mouse. |
| Cell type | Meiotic cells (e.g., spermatocytes, oocytes, plant meiocytes). |
| Stage | Pachytene of meiosis I. |
What Is GO:0005715?
According to the Gene Ontology, GO:0005715 late recombination nodule is defined as an electron dense structure that is associated with meiotic chromosomes in pachytene during meiosis I. In practice, late recombination nodules are cytological structures that mark the sites of reciprocal crossover events and are enriched in proteins that promote crossover formation, such as COSA-1 in C. elegans. They are distinct from early recombination nodules, which appear earlier and are associated with synapsis and recombination initiation.
Why Is late recombination nodule Important in Cell Biology?
Late recombination nodules are important because they provide a direct cytological readout of crossover formation, which is essential for accurate chromosome segregation and genetic diversity. Defects in crossover formation can lead to aneuploidy, infertility, and developmental disorders. In plants, the number and distribution of late recombination nodules are used to study recombination frequency and to inform breeding strategies. In animals, proteins such as CDK2 and COSA-1 are required for late recombination nodule formation and crossover completion, linking cell cycle regulation to meiotic recombination.
• Late recombination nodules mark reciprocal crossover events and are essential for faithful chromosome segregation.
• They are used as a cytological proxy for crossover frequency in plants and animals.
• Proteins such as COSA-1 in C. elegans are enriched at late recombination nodules and are required for crossover formation.
• CDK2 activity at crossover sites is necessary for late recombination nodule formation in mouse spermatocytes.
• Defects in late recombination nodule formation can cause meiotic arrest and infertility.
• Studying late recombination nodules helps understand the mechanisms of meiotic recombination and aneuploidy.
• They are relevant to plant breeding because recombination frequency affects genetic mapping and selection.
• Late recombination nodules are distinct from early nodules and provide insight into the two-step process of recombination.
• They are conserved structures across eukaryotes, from plants to mammals.
• Research on late recombination nodules informs reproductive medicine and cancer biology.
Structure and Composition of late recombination nodule
Electron-dense structure at pachytene
In simple terms: Late recombination nodules are dark, dense spots visible on meiotic chromosomes under an electron microscope.
Late recombination nodules are electron-dense structures associated with meiotic chromosomes during pachytene of meiosis I. They are typically observed as discrete, dense bodies on the synaptonemal complex and are considered the morphological manifestation of crossover events.
Enrichment of pro-crossover proteins
In simple terms: These nodules contain proteins that promote crossing over, such as COSA-1 in worms.
In C. elegans, the pro-crossover protein COSA-1 is enriched at late recombination nodules and is required for crossover formation. COSA-1 mediates the formation of a pro-crossover complex that promotes meiotic crossing over.
Association with chromosome cores
In simple terms: Late nodules sit on the protein cores of meiotic chromosomes.
Late recombination nodules are associated with the chromosome cores and chromatin at meiotic prophase. They are positioned on the synaptonemal complex, which forms between homologous chromosomes during pachytene.
Distinction from early recombination nodules
In simple terms: Late nodules are different from early nodules, which appear earlier and are involved in recombination initiation.
Early recombination nodules appear before synapsis is complete and are associated with recombination initiation, whereas late recombination nodules appear later and mark crossover sites. In maize, the pattern of synapsis and the distribution of early nodules are related to the number of late nodules and crossing over.
Regulation by CDK2 at crossover sites
In simple terms: A cell cycle kinase, CDK2, is active at crossover sites and helps late nodules form.
A novel function for CDK2 activity at meiotic crossover sites has been described in mouse spermatocytes. CDK2 activity is required for late recombination nodule formation and crossover completion, linking cell cycle regulation to meiotic recombination.
Key Genes Involved in GO:0005715 late recombination nodule
The following genes and proteins have been implicated in late recombination nodule formation and function based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| COSA-1 | Pro-crossover complex formation; enriched at late recombination nodules in C. elegans | Required for meiotic crossing over; marker for late nodules |
| CDK2 | Cell cycle kinase; activity at crossover sites required for late nodule formation in mouse | Links cell cycle regulation to meiotic recombination |
| SYN1 | Synaptonemal complex protein; component of chromosome cores | Structural component of meiotic chromosomes |
| SYCP1 | Synaptonemal complex transverse filament protein | Required for synapsis and recombination |
| SYCP2 | Synaptonemal complex protein | Structural role in meiotic chromosome cores |
| SYCP3 | Synaptonemal complex protein | Structural role in meiotic chromosome cores |
| MLH1 | Mismatch repair protein; marks late recombination nodules in plants | Cytological marker for crossovers |
| MLH3 | Mismatch repair protein; component of late nodules | Cytological marker for crossovers |
| HEI10 | E3 ubiquitin ligase; promotes crossover formation | Regulates late nodule formation |
| ZIP1 | Synaptonemal complex protein | Required for synapsis |
| ZIP2 | Synaptonemal complex protein | Required for synapsis |
| ZIP3 | Synaptonemal complex protein | Required for synapsis |
| ZIP4 | Synaptonemal complex protein | Required for synapsis |
| MER3 | Helicase; promotes crossover formation | Required for late nodule formation |
| MSH4 | MutS homolog; promotes crossover formation | Required for late nodule formation |
| MSH5 | MutS homolog; promotes crossover formation | Required for late nodule formation |
| RAD51 | Recombinase; early recombination nodule component | Recombination initiation |
| DMC1 | Meiosis-specific recombinase | Recombination initiation |
How Is late recombination nodule Regulated?
Late recombination nodule formation is regulated by pro-crossover proteins such as COSA-1 in C. elegans, which mediates the formation of a pro-crossover complex that promotes meiotic crossing over. In mouse spermatocytes, CDK2 activity at crossover sites is required for late recombination nodule formation and crossover completion. The number and distribution of late nodules are also influenced by the pattern of synapsis and the distribution of early recombination nodules, as shown in maize. These regulatory mechanisms ensure that crossovers are properly placed and that meiosis progresses accurately.
late recombination nodule and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CDK2 | Meiotic arrest and infertility | Knockout mouse spermatocytes |
| COSA-1 | Defective crossover formation | C. elegans knockout |
| MLH1 | Crossover defects; cancer predisposition (Lynch syndrome) | Knockout mouse or cell lines |
| MLH3 | Crossover defects | Knockout mouse |
| HEI10 | Crossover defects | Knockout mouse or plant models |
Meiotic defects and infertility
Defects in late recombination nodule formation can lead to meiotic arrest and infertility. For example, CDK2 activity at crossover sites is required for late recombination nodule formation in mouse spermatocytes, and its loss impairs crossover completion. Similarly, mutations in pro-crossover proteins such as COSA-1 in C. elegans disrupt crossover formation and late nodule assembly. These findings link late recombination nodule function to reproductive disorders.
Aneuploidy and developmental disorders
Failure to form crossovers properly can result in aneuploidy, which is associated with developmental disorders such as Down syndrome and with pregnancy loss. Late recombination nodules are cytological markers of crossovers, and their number and distribution are critical for accurate chromosome segregation. Studying late nodules helps understand the mechanisms underlying aneuploidy.
Cancer and genome stability
Meiotic recombination proteins are often related to DNA repair proteins that play roles in genome stability and cancer. While direct links between late recombination nodules and cancer are not well established, the pro-crossover machinery shares components with DNA repair pathways. Further research is needed to clarify any cancer relevance.
From late recombination nodule-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X localize to late recombination nodules? | Tagged knock-in (e.g., GFP) in C. elegans or mouse |
| Is gene X required for late nodule formation? | Knockout (e.g., CRISPR/Cas9) in mouse or C. elegans |
| Does a point mutation in gene X affect crossover frequency? | Point mutation knock-in in mouse |
| Does overexpression of gene X increase late nodules? | Overexpression transgenic model |
| How does CDK2 activity regulate late nodules? | Conditional knockout or chemical inhibition in mouse spermatocytes |
| What is the ultrastructure of late nodules? | Electron microscopy in plants or animals |
How to Study the late recombination nodule Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Electron microscopy | Presence and number of electron-dense nodules | Counting late recombination nodules in plants and animals |
| Immunofluorescence | Localization of pro-crossover proteins | Detecting MLH1 or COSA-1 foci |
| GFP tagging | Dynamic localization of proteins | Live imaging of late nodule assembly |
| CRISPR knockout | Requirement of a gene for late nodule formation | Functional analysis of candidate genes |
| RNAi knockdown | Gene function in C. elegans | Studying COSA-1 and other pro-crossover genes |
| Western blot | Protein expression levels | Validating knockout or overexpression |
| Quantitative image analysis | Number and distribution of nodules | Comparing crossover frequency across genotypes |
Electron microscopy
Electron microscopy is the primary method for visualizing late recombination nodules, as they are defined as electron-dense structures. This technique allows researchers to count and map nodules on meiotic chromosomes.
Immunofluorescence and protein tagging
Immunofluorescence using antibodies against pro-crossover proteins such as MLH1 or COSA-1, or tagging these proteins with fluorescent markers, allows specific detection of late recombination nodules. This approach is useful for co-localization studies.
Genetic perturbation and knockout models
Knockout or knockdown of candidate genes, such as COSA-1 in C. elegans or CDK2 in mouse, followed by cytological analysis, can determine whether a gene is required for late nodule formation.
Live-cell imaging
Live-cell imaging of tagged pro-crossover proteins can reveal the dynamics of late recombination nodule assembly and disassembly during pachytene.
How CRISPR Can Be Used to Study GO:0005715 late recombination nodule
Knockout
CRISPR/Cas9 knockout of genes such as COSA-1 in C. elegans or CDK2 in mouse can be used to test their requirement for late recombination nodule formation. Knockout models often show reduced crossover frequency and defective late nodules.
Point Mutation
Point mutations can be introduced to dissect specific domains or phosphorylation sites in pro-crossover proteins. For example, mutating CDK2 phosphorylation sites could test their role in late nodule formation.
Knock-in
Knock-in of fluorescent tags (e.g., GFP) at endogenous loci allows visualization of late recombination nodules in live cells. This approach is useful for tracking protein dynamics during meiosis.
Overexpression
Overexpression of pro-crossover proteins such as COSA-1 can be used to test whether increased protein levels lead to more late recombination nodules or altered crossover distribution.
How EDITGENE Supports late recombination nodule Research
Researchers studying late recombination nodule-related genes often need to determine whether a candidate gene is causally involved in meiotic recombination. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this research, from gene knockout to precise point mutations and knock-in tagging.
Contact EDITGENE today to design your custom CRISPR model for late recombination nodule research.
Frequently Asked Questions About late recombination nodule
What is a late recombination nodule?
A late recombination nodule is an electron-dense structure associated with meiotic chromosomes during pachytene of meiosis I, marking reciprocal crossover events.
What genes are involved in late recombination nodules?
Key genes include COSA-1 in C. elegans, CDK2 in mouse, and MLH1 in plants, among others.
What is the function of late recombination nodules?
They serve as cytological markers of crossover formation and are required for accurate chromosome segregation.
How are late recombination nodules different from early nodules?
Early nodules appear before synapsis is complete and are involved in recombination initiation, while late nodules appear later and mark crossovers.
What is the GO term for late recombination nodule?
The Gene Ontology term is GO:0005715, defined as an electron dense structure associated with meiotic chromosomes in pachytene during meiosis I.
Which proteins are enriched at late recombination nodules?
Pro-crossover proteins such as COSA-1 in C. elegans and MLH1 in plants are enriched at late nodules.
How can I study late recombination nodules in the lab?
Electron microscopy, immunofluorescence, and genetic perturbation (e.g., CRISPR knockout) are common methods.
What diseases are associated with defective late recombination nodules?
Defects can lead to meiotic arrest, infertility, and aneuploidy.
Is CDK2 involved in late recombination nodules?
Yes, CDK2 activity at crossover sites is required for late recombination nodule formation in mouse spermatocytes.
What model organisms are used to study late recombination nodules?
Common models include C. elegans, mouse, and maize.
Conclusion
Late recombination nodules (GO:0005715) are essential cytological structures that mark crossover events during meiosis I. Their formation requires pro-crossover proteins such as COSA-1 and is regulated by cell cycle kinases like CDK2. Studying late recombination nodules provides insights into meiotic recombination, fertility, and genome stability. Continued research using advanced CRISPR models and imaging techniques will further elucidate their molecular composition and regulation.
References
- 2. Anderson LK et al.. 2005. Recombination nodules in plants.. Cytogenet Genome Res 109(1-3):198-204 PMID: 15753577
- 3. Yang Y et al.. 2024. COSA-1 mediated pro-crossover complex formation promotes meiotic crossing over in C. elegans.. Nucleic Acids Res 52(8):4375-4392 PMID: 38412290
- 4. Moens PB et al.. 1998. Chromosome cores and chromatin at meiotic prophase.. Curr Top Dev Biol 37:241-62 PMID: 9352188
- 6. Palmer N et al.. 2020. A novel function for CDK2 activity at meiotic crossover sites.. PLoS Biol 18(10):e3000903 PMID: 33075054
- 7. Stack SM et al.. 2002. Crossing over as assessed by late recombination nodules is related to the pattern of synapsis and the distribution of early recombination nodules in maize.. Chromosome Res 10(4):329-45 PMID: 12199146
