GO:0000707 meiotic DNA recombinase assembly: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0000707 meiotic DNA recombinase assembly describes the aggregation, arrangement and bonding together of strand exchange proteins (recombinases) into higher order oligomers on single-stranded DNA during meiosis.
• The two central recombinases are RAD51 and the meiosis-specific DMC1, which form helical filaments on single-stranded DNA to catalyze homologous recombination.
• Accessory factors such as BRCA2, MEILB2, BRME1, SPIDR, FIGNL1 and SOX30 regulate the assembly, stability and disassembly of these recombinase filaments [1,2,5,6,7,8].
• Defects in meiotic recombinase assembly cause meiotic arrest, infertility and genome instability, and are linked to cancer predisposition [1,5,7].
• CRISPR knockout, point-mutation, knock-in and overexpression models are essential to dissect the causal roles of these genes in meiosis [1,3,4,5,6,7,8].
• EDITGENE provides end-to-end CRISPR services, including library screening and bioinformatics, to accelerate research on meiotic DNA recombinase assembly.
Description
Meiotic DNA recombinase assembly (GO:0000707) is the biological process in which strand exchange proteins, known as recombinases, aggregate, arrange and bond together to form higher order oligomers on single-stranded DNA during meiosis. This process is a prerequisite for homologous recombination, the mechanism that ensures faithful chromosome segregation and genetic diversity in gametes. The core recombinases RAD51 and DMC1 assemble into helical filaments on single-stranded DNA, a step that is tightly regulated by a suite of accessory proteins including BRCA2, MEILB2, BRME1, SPIDR, FIGNL1 and SOX30 [1,2,5,6,7,8]. Understanding how these filaments assemble is fundamental to reproductive biology and cancer research, because errors in this process lead to meiotic arrest, infertility and genome instability [1,5,7]. Researchers studying meiosis rely on precise genetic models to determine the causal contribution of each factor to recombinase assembly [3,4,5,6,7,8].
meiotic DNA recombinase assembly At A Glance
| GO ID | GO:0000707 |
|---|---|
| GO term | meiotic DNA recombinase assembly |
| Ontology | biological_process |
| Synonym | None |
| Major function | Assembly of recombinase oligomers on single-stranded DNA during meiosis |
| Key recombinases | RAD51, DMC1 |
| Key regulators | BRCA2, MEILB2, BRME1, SPIDR, FIGNL1, SOX30 |
| Associated process | Homologous recombination |
| Research impact | Infertility, cancer predisposition, genome stability |
What Is GO:0000707?
According to the Gene Ontology, meiotic DNA recombinase assembly (GO:0000707) is defined as the aggregation, arrangement and bonding together of strand exchange proteins (recombinases) to form higher order oligomers on single-stranded DNA during meiosis. In simpler terms, it is the step where individual recombinase proteins come together on single-stranded DNA to build the functional filament that performs strand exchange.
Why Is meiotic DNA recombinase assembly Important in Cell Biology?
Meiotic DNA recombinase assembly is essential for homologous recombination during meiosis, the process that generates genetic diversity and ensures accurate chromosome segregation. Failure of this assembly leads to meiotic arrest, infertility and genome instability, and mutations in assembly factors are associated with cancer predisposition [1,5,7]. Studying this process provides insights into fundamental mechanisms of DNA repair and has direct implications for reproductive medicine and oncology [3,6,8].
• Ensures faithful homologous recombination and chromosome segregation during meiosis.
• Defects cause meiotic arrest and infertility in mammals [1,7].
• Mutations in assembly factors are linked to cancer predisposition.
• Provides mechanistic insight into RAD51/DMC1 filament dynamics.
• Reveals regulatory roles of BRCA2, MEILB2, BRME1 and SPIDR [1,6,8].
• Informs development of reproductive and oncology therapeutics.
• Serves as a model for understanding genome stability.
• Guides CRISPR-based functional studies in meiosis [4,7].
What Happens During meiotic DNA recombinase assembly?
Initiation and DNA-driven condensation
In simple terms: The process starts when DNA ends are processed and the break machinery condenses on DNA.
During meiosis, programmed DNA double-strand breaks are formed and resected to produce single-stranded DNA. DNA-driven condensation assembles the meiotic DNA break machinery, creating a platform for subsequent recombinase loading.
Loading of RAD51 and DMC1
In simple terms: The recombinase proteins RAD51 and DMC1 are loaded onto single-stranded DNA.
RAD51 and the meiosis-specific DMC1 are the central recombinases. RAD51 facilitates filament assembly of DMC1, and together they form helical filaments on single-stranded DNA. In Arabidopsis, DMC1 attenuates RAD51-mediated recombination, indicating a regulatory interplay.
Accessory factor-mediated regulation
In simple terms: Helper proteins control where and when the recombinase filaments form.
BRCA2, MEILB2 and BRME1 cooperate to regulate recombinase assembly. MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2 binding, and BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination [6,8]. SPIDR is also required for homologous recombination during mammalian meiosis.
Filament remodeling and disassembly
In simple terms: The filaments are remodeled and removed to allow downstream steps.
FIGNL1, an AAA+ ATPase, remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination, ensuring proper filament turnover. SOX30 governs synaptonemal complex assembly and homologous recombination in male meiosis, linking recombinase assembly to downstream synapsis.
Key Genes Involved in GO:0000707 meiotic DNA recombinase assembly
The following genes and proteins are central to meiotic DNA recombinase assembly and are frequently studied using CRISPR models.
| Gene | Major Role | Research Relevance |
|---|---|---|
| RAD51 | Core recombinase; forms filaments on ssDNA | Essential for homologous recombination; knockout causes meiotic arrest |
| DMC1 | Meiosis-specific recombinase; facilitates filament assembly | Required for interhomolog recombination; knockout leads to infertility [3,4] |
| BRCA2 | Loads RAD51 onto ssDNA; interacts with MEILB2-BRME1 | Mutations linked to cancer and meiotic defects [6,8] |
| MEILB2 | Forms V-shaped DNA clamp with BRME1 upon BRCA2 binding | Regulates recombinase assembly; knockout impairs meiosis |
| BRME1 | Partners with MEILB2; promotes BRCA2 ring disassembly | Essential for homologous recombination; knockout causes meiotic arrest |
| SPIDR | Required for homologous recombination during mammalian meiosis | Knockout leads to meiotic defects and infertility |
| FIGNL1 | AAA+ ATPase; remodels RAD51 and DMC1 filaments | Regulates filament turnover; knockout affects replication and recombination |
| SOX30 | Governs synaptonemal complex assembly and homologous recombination | Knockout causes male meiotic arrest |
| HSF2BP | Forms oligomeric ring with BRCA2; regulated by BRME1 | Modulates BRCA2 function in recombination |
| RAD51AP1 | Accessory factor for RAD51-mediated recombination | Potential regulator of filament assembly |
| RAD54 | Motor protein that remodels recombinase filaments | Facilitates strand exchange |
| RPA | Single-stranded DNA-binding protein | Protects ssDNA and influences recombinase loading |
| MRE11 | Part of MRN complex; initiates resection | Required for DNA break processing |
| RAD50 | Part of MRN complex; DNA break repair | Facilitates early steps of recombination |
| NBS1 | Part of MRN complex; DNA damage response | Links break recognition to recombinase assembly |
| HOP2 | Meiosis-specific accessory factor | Promotes DMC1-mediated recombination |
| MND1 | Partners with HOP2 | Stabilizes recombinase filaments |
How Is meiotic DNA recombinase assembly Regulated?
Meiotic DNA recombinase assembly is regulated by a network of accessory proteins. BRCA2, MEILB2 and BRME1 control the loading and disassembly of RAD51 filaments, with BRME1 promoting the disassembly of BRCA2-HSF2BP oligomeric rings [6,8]. FIGNL1 remodels RAD51 and DMC1 filaments, ensuring proper turnover. SPIDR is required for homologous recombination in mammalian meiosis. SOX30 governs synaptonemal complex assembly and homologous recombination, linking recombinase assembly to downstream synapsis. Additionally, DMC1 attenuates RAD51-mediated recombination in Arabidopsis, indicating a regulatory balance between the two recombinases.
meiotic DNA recombinase assembly and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SPIDR | Meiotic defects and infertility | Knockout mouse model |
| SOX30 | Male meiotic arrest | Knockout mouse model |
| BRCA2 | Cancer predisposition and meiotic defects | Knock-in point mutation models [6,8] |
| FIGNL1 | Genome instability and cancer | Knockout and overexpression cell models |
| DMC1 | Infertility and recombination defects | Knockout and point mutation models [3,4] |
Infertility and meiotic arrest
Defects in meiotic DNA recombinase assembly cause meiotic arrest and infertility. Knockout of SPIDR in mice leads to meiotic defects and infertility. SOX30 knockout causes male meiotic arrest due to impaired synaptonemal complex assembly and homologous recombination.
Cancer predisposition
Mutations in genes regulating recombinase assembly, such as BRCA2 and FIGNL1, are associated with cancer predisposition. BRCA2-HSF2BP oligomeric ring disassembly by BRME1 is critical for homologous recombination, and its disruption can lead to genome instability. FIGNL1 remodels RAD51 and DMC1 filaments, and its dysfunction may contribute to cancer.
Genome instability syndromes
Impaired recombinase assembly leads to genome instability, a hallmark of cancer and premature aging. DNA-driven condensation of the meiotic break machinery is essential for proper recombination, and its failure can cause chromosomal abnormalities.
From meiotic DNA recombinase assembly-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does SPIDR loss cause meiotic arrest? | SPIDR knockout mouse |
| How does DMC1 regulate RAD51 filament assembly? | DMC1 knockout and point mutation cell lines [3,4] |
| What is the role of BRME1 in BRCA2 ring disassembly? | BRME1 knockout and knock-in models |
| How does FIGNL1 remodel RAD51 filaments? | FIGNL1 overexpression and knockout cells |
| Does SOX30 govern synaptonemal complex assembly? | SOX30 knockout mouse |
| How does MEILB2-BRME1 clamp DNA? | MEILB2-BRME1 knock-in tagged models |
How to Study the meiotic DNA recombinase assembly Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Loss-of-function effects | Identify essential genes for recombinase assembly |
| Point mutation | Specific residue function | Dissect protein-protein interactions |
| Knock-in tagging | Protein localization and dynamics | Visualize filament assembly |
| Overexpression | Gain-of-function effects | Study filament remodeling |
| Proteomics | Protein interactions | Identify assembly factors |
| Live-cell imaging | Real-time filament dynamics | Monitor recombinase assembly |
| CRISPR library screening | Genome-wide functional analysis | Discover novel regulators |
| Bioinformatics | Data integration and pathway analysis | Interpret screening results |
CRISPR knockout screens
Genome-wide CRISPR knockout screens can identify genes required for meiotic DNA recombinase assembly. For example, knockout of SPIDR revealed its requirement for homologous recombination in mammalian meiosis.
Point mutation and knock-in models
Point mutations and knock-in tags allow precise dissection of protein function. Knock-in of tagged DMC1 or RAD51 enables visualization of filament assembly. Point mutations in BRCA2 can disrupt its interaction with MEILB2-BRME1.
Proteomics and interactomics
Proteomic approaches identify interaction partners of recombinases. MEILB2-BRME1 was shown to form a V-shaped DNA clamp upon BRCA2 binding using structural and biochemical methods.
Imaging and live-cell analysis
Fluorescence microscopy of tagged recombinases allows real-time visualization of filament assembly on single-stranded DNA. FIGNL1-mediated remodeling of RAD51 and DMC1 filaments was demonstrated using imaging.
How CRISPR Can Be Used to Study GO:0000707 meiotic DNA recombinase assembly
Knockout
CRISPR knockout of genes such as SPIDR, SOX30, DMC1 and FIGNL1 has been used to demonstrate their essential roles in meiotic DNA recombinase assembly and homologous recombination [1,3,5,7].
Point Mutation
Point mutations introduced by CRISPR can disrupt specific protein interactions, such as the BRCA2-MEILB2-BRME1 interface, to study their role in recombinase assembly [6,8].
Knock-in
Knock-in of fluorescent tags or epitope tags allows visualization and purification of recombinase complexes, as shown for DMC1 and RAD51.
Overexpression
Overexpression of FIGNL1 or DMC1 can reveal dominant effects on filament remodeling and recombination [4,5].
How EDITGENE Supports meiotic DNA recombinase assembly Research
Researchers studying meiotic DNA recombinase assembly-related genes often need to determine whether a candidate gene is causally involved in the process. EDITGENE provides comprehensive CRISPR services to generate knockout, point-mutation, knock-in and overexpression models, as well as library screening and bioinformatics support, to accelerate discoveries in meiosis and genome stability.
Contact EDITGENE today to design your custom CRISPR model for meiotic DNA recombinase assembly research.
Frequently Asked Questions About meiotic DNA recombinase assembly
What is meiotic DNA recombinase assembly?
It is the process defined by GO:0000707 where strand exchange proteins (recombinases) aggregate, arrange and bond together to form higher order oligomers on single-stranded DNA during meiosis.
What genes are involved in meiotic DNA recombinase assembly?
Key genes include RAD51, DMC1, BRCA2, MEILB2, BRME1, SPIDR, FIGNL1 and SOX30 [1,3,5,6,7,8].
Why is meiotic DNA recombinase assembly important?
It is essential for homologous recombination, genetic diversity and faithful chromosome segregation; defects cause infertility and genome instability [1,5,7].
What diseases are linked to defects in meiotic DNA recombinase assembly?
Infertility, meiotic arrest and cancer predisposition are linked to defects in this process [1,5,7,8].
How is meiotic DNA recombinase assembly regulated?
It is regulated by accessory proteins such as BRCA2, MEILB2, BRME1, FIGNL1 and SPIDR, which control filament loading, stability and disassembly [1,5,6,8].
What is the role of DMC1 in meiotic DNA recombinase assembly?
DMC1 is a meiosis-specific recombinase that facilitates filament assembly and attenuates RAD51-mediated recombination [3,4].
How can CRISPR be used to study meiotic DNA recombinase assembly?
CRISPR knockout, point mutation, knock-in and overexpression models allow functional dissection of genes involved in this process [1,3,4,5,6,7,8].
What model systems are used to study meiotic DNA recombinase assembly?
Mouse models, Arabidopsis and cell lines are commonly used, with knockouts of SPIDR, SOX30, DMC1 and FIGNL1 [1,3,4,5,7].
What is the role of BRCA2 in meiotic DNA recombinase assembly?
BRCA2 loads RAD51 onto single-stranded DNA and interacts with MEILB2-BRME1 to regulate filament assembly [6,8].
How does FIGNL1 regulate recombinase filaments?
FIGNL1 is an AAA+ ATPase that remodels RAD51 and DMC1 filaments, ensuring proper turnover during meiosis.
Conclusion
Meiotic DNA recombinase assembly (GO:0000707) is a tightly regulated process essential for homologous recombination and fertility. The interplay between RAD51, DMC1 and accessory factors such as BRCA2, MEILB2, BRME1, SPIDR, FIGNL1 and SOX30 ensures proper filament formation and genome stability [1,3,5,6,7,8]. Understanding this process has direct implications for infertility and cancer research, and CRISPR-based models are indispensable for dissecting the causal roles of each factor [1,3,4,5,6,7,8].
References
- 1. Huang T et al.. 2023. SPIDR is required for homologous recombination during mammalian meiosis.. Nucleic Acids Res 51(8):3855-3868 PMID: 36938872
- 2. Claeys Bouuaert C et al.. 2021. DNA-driven condensation assembles the meiotic DNA break machinery.. Nature 592(7852):144-149 PMID: 33731927
- 3. Lan WH et al.. 2020. Rad51 facilitates filament assembly of meiosis-specific Dmc1 recombinase.. Proc Natl Acad Sci U S A 117(21):11257-11264 PMID: 32404423
- 4. Da Ines O et al.. 2022. DMC1 attenuates RAD51-mediated recombination in Arabidopsis.. PLoS Genet 18(8):e1010322 PMID: 36007010
- 5. Ito M et al.. 2023. FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination.. Nat Commun 14(1):6857 PMID: 37891173
- 6. Gurusaran M et al.. 2024. MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination.. Nat Commun 15(1):6552 PMID: 39095423
- 7. Liu K et al.. 2026. SOX30 Governs Synaptonemal Complex Assembly and Homologous Recombination in Male Meiosis.. Cell Prolif 59(6):e70158 PMID: 41467312
- 8. Ghouil R et al.. 2023. BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination.. Sci Adv 9(43):eadi7352 PMID: 37889963
