GO:1990918 double-strand break repair involved in meiotic recombination: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1990918 describes the repair of programmed DNA double-strand breaks (DSBs) by homologous and nonhomologous mechanisms to form a continuous DNA helix that contributes to reciprocal meiotic recombination.
• Meiotic DSB repair is essential for faithful chromosome segregation and genetic diversity; defects cause infertility, aneuploidy, and developmental disorders.
• SPIDR is a recently identified factor required for homologous recombination during mammalian meiosis, highlighting new components of this pathway.
• The process is tightly regulated by cell-cycle kinases, post-transcriptional modifiers such as hnRNPA2B1, and PARP1-dependent repair in late pachytene spermatocytes.
• BRCA- and ATM-mediated DSB repair pathways influence ovarian aging and reproductive lifespan, linking meiotic recombination to reproductive medicine.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal dissection of genes in this GO term for reproductive and cancer research.
Description
GO:1990918, double-strand break repair involved in meiotic recombination, is a biological process that encompasses the repair of programmed DNA double-strand breaks (DSBs) via homologous and nonhomologous mechanisms to reform a continuous DNA helix, thereby contributing to reciprocal meiotic recombination. This process is fundamental to meiosis, ensuring both genetic diversity and accurate chromosome segregation. Errors in meiotic DSB repair lead to gametogenic failure, aneuploidy, and infertility, making it a critical area of reproductive biology and genetics. Recent studies have expanded the list of proteins required for this process in mammals, including SPIDR, which is essential for homologous recombination during meiosis. In plants, engineering meiotic recombination pathways has become a target for crop improvement, underscoring the broad relevance of this GO term. Understanding the molecular players and regulatory layers of meiotic DSB repair is therefore central to both basic and translational research.
double-strand break repair involved in meiotic recombination At A Glance
| GO ID | GO:1990918 |
|---|---|
| GO term | double-strand break repair involved in meiotic recombination |
| Ontology | biological_process |
| Synonym | None |
| Major function | Repair of programmed meiotic DSBs to form a continuous DNA helix, enabling reciprocal recombination |
| Related processes | Homologous recombination, nonhomologous end joining, meiotic recombination |
| Key cellular context | Meiosis, specifically prophase I (leptotene to pachytene) |
| Disease relevance | Infertility, aneuploidy, ovarian aging, cancer predisposition |
What Is GO:1990918?
According to the Gene Ontology, GO:1990918 is defined as the repair of double-strand breaks in DNA via homologous and nonhomologous mechanisms to reform a continuous DNA helix that contributes to reciprocal meiotic recombination. In simpler terms, it is the cellular process that fixes deliberate breaks in DNA during meiosis, using either a template-based (homologous) or direct rejoining (nonhomologous) mechanism, so that chromosomes can exchange genetic material and segregate properly.
Why Is double-strand break repair involved in meiotic recombination Important in Cell Biology?
Meiotic DSB repair is essential for sexual reproduction because it generates genetic diversity and ensures the physical connections between homologous chromosomes that are required for their proper segregation. Defects in this process cause meiotic arrest, germ cell loss, and aneuploidy, which manifest as infertility, recurrent pregnancy loss, and developmental syndromes such as Down syndrome. In addition, the same repair machinery is linked to cancer predisposition and reproductive aging; for example, BRCA- and ATM-mediated DSB repair influences ovarian aging. Understanding GO:1990918 therefore has direct implications for reproductive medicine, cancer biology, and agricultural biotechnology.
• Ensures faithful chromosome segregation by forming crossovers that hold homologs together.
• Generates genetic diversity through reciprocal recombination.
• Prevents aneuploidy and germ cell death; defects cause infertility.
• SPIDR is required for homologous recombination in mammalian meiosis, and its loss impairs fertility.
• BRCA- and ATM-mediated DSB repair affects ovarian aging and reproductive lifespan.
• PARP1-dependent DSB repair operates in late pachytene spermatocytes, linking DNA repair to meiotic progression.
• Post-transcriptional regulation by hnRNPA2B1 modulates late pachytene progression in male meiosis.
• Engineering meiotic recombination pathways in crops can enhance breeding efficiency.
• Nucleolar Cdc14 function connects meiotic recombination to cell cycle control.
• Provides a mechanistic basis for understanding cancer-associated mutations in recombination genes.
What Happens During double-strand break repair involved in meiotic recombination?
Initiation of Meiotic DSBs
In simple terms: The cell deliberately cuts its own DNA to start the process of genetic shuffling.
Meiotic recombination begins with the programmed formation of DNA double-strand breaks (DSBs) by the SPO11 topoisomerase-like enzyme. These breaks are introduced in early prophase I and are essential for subsequent repair and crossover formation. The number and distribution of DSBs are tightly regulated to ensure at least one crossover per chromosome arm, which is necessary for proper segregation.
Resection and Homology Search
In simple terms: The broken DNA ends are chewed back to create single-stranded tails that search for a matching sequence on the homologous chromosome.
After DSB formation, the 5' ends are resected to generate 3' single-stranded DNA overhangs. These overhangs are bound by recombinases such as RAD51 and DMC1, which facilitate invasion of the homologous duplex to form a displacement loop (D-loop). This homology search and strand invasion is the central step of homologous recombination during meiosis. SPIDR has been shown to be required for this homologous recombination step in mammalian meiosis.
Crossover Formation and Resolution
In simple terms: The DNA strands are exchanged and cut to produce crossovers, which are physical links between chromosomes.
Following strand invasion, the D-loop is extended and second-end capture leads to the formation of double Holliday junctions or alternative intermediates. These intermediates are resolved by structure-selective endonucleases to yield either crossovers or non-crossovers. Crossovers are essential for the formation of chiasmata, which hold homologous chromosomes together until anaphase I. In mammals, crossover formation is tightly regulated and requires a suite of proteins including MLH1 and MLH3.
Nonhomologous Repair Pathways
In simple terms: Sometimes the breaks are repaired without using a template, by simply joining the ends back together.
In addition to homologous recombination, meiotic DSBs can be repaired by nonhomologous mechanisms such as nonhomologous end joining (NHEJ). While NHEJ is generally error-prone, it may serve as a backup pathway in meiosis. The balance between homologous and nonhomologous repair is critical for maintaining genome integrity and ensuring proper meiotic progression. PARP1-dependent repair has been observed in late pachytene spermatocytes, suggesting a role for alternative repair pathways in meiosis.
Regulation by Cell Cycle and Post-Transcriptional Modifiers
In simple terms: The timing and efficiency of repair are controlled by cell cycle signals and RNA modifications.
Meiotic DSB repair is coordinated with the cell cycle. For example, the nucleolar protein Cdc14 regulates meiotic recombination and cell cycle progression. Post-transcriptional regulation by the m6A reader hnRNPA2B1 modulates late pachytene progression in male meiosis, affecting the expression of repair factors. These layers of regulation ensure that repair occurs at the right time and place.
Key Genes Involved in GO:1990918 double-strand break repair involved in meiotic recombination
The following genes and proteins are central to double-strand break repair involved in meiotic recombination, as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SPO11 | Catalyzes meiotic DSB formation | Essential for initiation; knockout causes meiotic arrest |
| RAD51 | Recombinase for strand invasion | Key homologous recombination factor; studied in infertility |
| DMC1 | Meiosis-specific recombinase | Required for interhomolog recombination |
| SPIDR | Required for homologous recombination in mammalian meiosis | Newly identified; knockout impairs fertility |
| MLH1 | Mismatch repair protein involved in crossover formation | Marker for crossovers; mutations linked to cancer and infertility |
| MLH3 | Part of MutLgamma complex for crossover resolution | Required for normal crossover frequency |
| BRCA1 | DNA repair and recombination | Linked to ovarian aging and cancer |
| BRCA2 | Homologous recombination mediator | Involved in ovarian aging and cancer |
| ATM | DSB signaling kinase | Regulates repair and ovarian aging |
| PARP1 | Poly(ADP-ribose) polymerase; DSB repair | Active in late pachytene spermatocytes |
| hnRNPA2B1 | m6A reader; post-transcriptional regulation | Modulates late pachytene progression |
| CDC14 | Nucleolar phosphatase; cell cycle control | Regulates meiotic recombination |
| Cdc14 | Nucleolar role in meiotic recombination | Insights into cell cycle control |
| RAD51C | Homologous recombination | Associated with Fanconi anemia and infertility |
| RAD51D | Homologous recombination | Associated with cancer predisposition |
| MSH4 | Crossover formation | Required for chiasma formation |
| MSH5 | Crossover formation | Required for chiasma formation |
How Is double-strand break repair involved in meiotic recombination Regulated?
The process of double-strand break repair involved in meiotic recombination is regulated at multiple levels. Cell cycle kinases, including CDK1 and ATM, control the timing of DSB formation and repair. Post-transcriptional regulation by the m6A reader hnRNPA2B1 modulates late pachytene progression in male meiosis, affecting the expression of repair factors. PARP1-dependent repair pathways are active in late pachytene spermatocytes, suggesting a role for poly(ADP-ribosyl)ation in meiotic DSB repair. Additionally, the nucleolar protein Cdc14 regulates meiotic recombination and cell cycle control, linking nucleolar function to repair. These regulatory layers ensure that recombination is completed accurately and in a timely manner.
double-strand break repair involved in meiotic recombination and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SPIDR | Infertility, meiotic arrest | Knockout mouse, spermatocyte culture |
| BRCA1 | Ovarian aging, breast/ovarian cancer | Conditional knockout mouse, iPSC-derived germ cells |
| ATM | Ovarian aging, ataxia-telangiectasia | Knockout mouse, patient fibroblasts |
| MLH1 | Non-obstructive azoospermia, cancer | Knockout mouse, testis organoids |
| PARP1 | Meiotic progression defects | Knockout mouse, irradiated spermatocytes |
Meiotic Recombination Defects and Infertility
Mutations in genes required for meiotic DSB repair cause azoospermia, premature ovarian insufficiency, and recurrent pregnancy loss. For example, SPIDR is required for homologous recombination during mammalian meiosis, and its deficiency leads to impaired fertility. Defects in crossover formation genes such as MLH1 and MLH3 are associated with non-obstructive azoospermia.
Ovarian Aging and Reproductive Lifespan
BRCA- and ATM-mediated DSB repair pathways influence ovarian aging. Women with BRCA mutations exhibit reduced ovarian reserve and earlier menopause, linking meiotic recombination capacity to reproductive lifespan.
Cancer Predisposition
Many genes involved in meiotic recombination, such as BRCA1, BRCA2, and RAD51 paralogs, are also tumor suppressors. Their dysfunction leads to genomic instability and cancer predisposition, highlighting the dual role of these repair factors in meiosis and somatic maintenance.
Aneuploidy and Developmental Disorders
Failure of meiotic recombination leads to aneuploidy, which is a leading cause of miscarriage and developmental disorders such as Down syndrome. Proper crossover formation is essential for accurate chromosome segregation.
From double-strand break repair involved in meiotic recombination-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X cause meiotic DSB repair defects? | Knockout cell line (e.g., HEK293T, mouse ES cells) |
| Does a specific mutation affect protein function? | Point mutation knock-in via CRISPR |
| How does a repair factor localize during meiosis? | Tagged knock-in (e.g., GFP) in mouse germ cells |
| Can overexpression rescue a repair defect? | Overexpression cell model |
| What is the role of a gene in crossover formation? | Knockout mouse and spermatocyte spreads |
| How does a regulatory RNA modification affect repair? | Knockout of hnRNPA2B1 in mouse testis |
How to Study the double-strand break repair involved in meiotic recombination Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screen | Gene essentiality for meiotic DSB repair | Identify novel repair factors |
| Immunofluorescence of spreads | DSB repair foci and crossovers | Assess recombination defects in mutants |
| In vitro recombination assay | Biochemical activity of recombinases | Mechanistic studies of strand invasion |
| RNA-seq | Transcriptional changes | Analyze gene expression in repair mutants |
| Proteomics | Protein abundance and modifications | Identify post-translational regulation |
| m6A-seq | RNA methylation sites | Study post-transcriptional regulation |
| Live-cell imaging | Dynamic recruitment of repair proteins | Visualize repair foci in real time |
| Yeast two-hybrid | Protein-protein interactions | Map repair complex assembly |
CRISPR Screens for Meiotic Repair Genes
Genome-wide CRISPR knockout screens can identify novel genes required for meiotic DSB repair. Libraries targeting DNA repair genes are particularly useful for uncovering factors that affect recombination efficiency and crossover distribution.
Imaging of Meiotic Prophase
Immunofluorescence staining of meiotic chromosome spreads for markers such as RAD51, DMC1, and MLH1 allows visualization of DSB repair foci and crossovers. This method is widely used to assess recombination defects in knockout models.
Biochemical Assays for Recombination
In vitro reconstitution assays using purified proteins can dissect the biochemical mechanisms of strand invasion, D-loop formation, and resolution. These assays are essential for understanding the catalytic steps of meiotic recombination.
Transcriptomics and Proteomics
RNA-seq and proteomics can reveal changes in gene expression and protein abundance in response to repair defects. For example, m6A-seq and RIP-seq have been used to study hnRNPA2B1-mediated regulation of meiotic progression.
How CRISPR Can Be Used to Study GO:1990918 double-strand break repair involved in meiotic recombination
Knockout
CRISPR knockout of genes such as SPIDR, RAD51, or MLH1 in cell lines or mouse models can reveal their essential roles in meiotic DSB repair. For example, SPIDR knockout mice exhibit impaired homologous recombination and fertility defects. Knockout cell models are valuable for studying the loss-of-function phenotypes of repair genes.
Point Mutation
Introducing specific point mutations via CRISPR base editing or homology-directed repair allows researchers to dissect the functional domains of repair proteins. For instance, mutations in the catalytic site of SPO11 or in the BRCA1 BRCT domain can be modeled to understand their impact on meiotic recombination.
Knock-in
Knock-in of tagged versions of repair proteins (e.g., GFP-RAD51) enables live-cell imaging and proteomic analysis. This approach has been used to track the localization and dynamics of recombination factors during meiosis.
Overexpression
Overexpression of repair genes or their dominant-negative variants can test sufficiency and rescue. For example, overexpression of SPIDR in SPIDR-deficient cells can restore homologous recombination, confirming its specific role. Overexpression models are also useful for studying gene dosage effects in meiosis.
How EDITGENE Supports double-strand break repair involved in meiotic recombination Research
Researchers studying double-strand break repair involved in meiotic recombination-related genes often need to determine whether a candidate gene is causally involved in the repair process, and to dissect its precise function using robust genetic models. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for double-strand break repair involved in meiotic recombination research.
Frequently Asked Questions About double-strand break repair involved in meiotic recombination
What is GO:1990918?
GO:1990918 is the Gene Ontology term for double-strand break repair involved in meiotic recombination, defined as the repair of DNA double-strand breaks via homologous and nonhomologous mechanisms to reform a continuous DNA helix that contributes to reciprocal meiotic recombination.
What genes are involved in double-strand break repair involved in meiotic recombination?
Key genes include SPO11, RAD51, DMC1, SPIDR, MLH1, MLH3, BRCA1, BRCA2, ATM, and PARP1, among others.
Why is meiotic recombination important?
It generates genetic diversity and ensures proper chromosome segregation; defects cause infertility and aneuploidy.
How does SPIDR function in meiosis?
SPIDR is required for homologous recombination during mammalian meiosis, and its loss impairs fertility.
What is the role of BRCA1 in meiotic recombination?
BRCA1 is involved in DNA repair and recombination, and BRCA-mediated pathways influence ovarian aging.
How is meiotic DSB repair regulated?
It is regulated by cell cycle kinases, post-transcriptional modifiers such as hnRNPA2B1, and PARP1-dependent pathways.
What diseases are linked to defects in meiotic DSB repair?
Infertility, azoospermia, ovarian aging, aneuploidy, and cancer predisposition.
What model systems are used to study meiotic recombination?
Mouse models, yeast, and CRISPR-engineered cell lines are commonly used.
Can CRISPR be used to study meiotic recombination genes?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable functional dissection of these genes.
What methods are used to measure meiotic DSB repair?
Immunofluorescence of chromosome spreads, in vitro recombination assays, RNA-seq, and proteomics.
Conclusion
GO:1990918, double-strand break repair involved in meiotic recombination, is a fundamental biological process that ensures genetic diversity and faithful chromosome segregation. Its molecular players, including SPO11, RAD51, DMC1, SPIDR, and BRCA1/2, are critical for fertility and genome stability, and their dysfunction is linked to infertility, aneuploidy, and cancer. Continued research using CRISPR-based models and advanced omics will further illuminate the mechanisms and regulation of this process, with important implications for reproductive medicine and agriculture.
References
- 1. Raina VB et al.. 2025. Biochemical Mechanisms of Genetic Recombination and DNA Repair.. Annu Rev Biochem 94(1):161-193 PMID: 40153609
- 2. Xie C et al.. 2022. Meiotic recombination: insights into its mechanisms and its role in human reproduction with a special focus on non-obstructive azoospermia.. Hum Reprod Update 28(6):763-797 PMID: 35613017
- 3. Huang T et al.. 2023. SPIDR is required for homologous recombination during mammalian meiosis.. Nucleic Acids Res 51(8):3855-3868 PMID: 36938872
- 4. Fayos I et al.. 2019. Engineering meiotic recombination pathways in rice.. Plant Biotechnol J 17(11):2062-2077 PMID: 31199561
- 5. Turan V et al.. 2020. BRCA-related ATM-mediated DNA double-strand break repair and ovarian aging.. Hum Reprod Update 26(1):43-57 PMID: 31822904
- 6. Yin L et al.. 2025. m(6)A Reader hnRNPA2B1 Modulates Late Pachytene Progression in Male Meiosis Through Post-Transcriptional Control.. Adv Sci (Weinh) 12(38):e06600 PMID: 40720760
- 7. Ahmed EA et al.. 2021. Parp1-Dependent DNA Double-Strand Break Repair in Irradiated Late Pachytene Spermatocytes.. DNA Cell Biol 40(2):209-218 PMID: 33337266
- 8. Alonso-Ramos P et al.. 2024. Decoding the Nucleolar Role in Meiotic Recombination and Cell Cycle Control: Insights into Cdc14 Function.. Int J Mol Sci 25(23) PMID: 39684572
