GO:0000711 meiotic DNA repair synthesis: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0000711 meiotic DNA repair synthesis is defined as the synthesis of DNA that proceeds from a broken 3-prime single-strand DNA end using the homologous intact duplex as the template during meiosis.
• This process is a central step of meiotic recombination that helps convert programmed double-strand breaks into crossover and noncrossover products.
• Recombination-coupled DNA synthesis is required for post-invasion steps in both meiotic crossover and noncrossover formation.
• The DNA helicase/nuclease Dna2 removes toxic ssDNA-RPA filaments that arise from meiotic recombination-associated DNA synthesis.
• Meiotic double-strand break repair DNA synthesis tracts can be mapped genome-wide, for example in Arabidopsis thaliana, providing a quantitative readout of the process.
• Proteins such as SYCP2, BCAS2, hnRNPH1, Mre11-Rad50-Nbs1 and Tel1/ATM influence DNA repair, synapsis and break formation in meiotic prophase I.
Description
Meiotic DNA repair synthesis (GO:0000711) is the biological process in which DNA is synthesized from a broken 3-prime single-strand DNA end using the homologous intact duplex as the template during meiosis. It is a specialized form of repair synthesis that occurs after strand invasion and is mechanistically coupled to the recombination machinery that processes programmed meiotic double-strand breaks. Because meiosis must both repair breaks and generate genetic diversity, the synthesis step is tightly coordinated with crossover and noncrossover formation. Researchers study this process to understand how homologous recombination is completed, how genome stability is maintained in germ cells, and how defects in meiotic repair synthesis may contribute to infertility and developmental disorders. Recent work has also shown that recombination-coupled DNA synthesis facilitates post-invasion steps in meiotic crossover and noncrossover formations, making it a key node for mechanistic and quantitative studies. In addition, genome-wide mapping of meiotic double-strand break repair DNA synthesis tracts in Arabidopsis thaliana has provided a tractable system to measure where and how much repair synthesis occurs.
meiotic DNA repair synthesis At A Glance
| GO ID | GO:0000711 |
|---|---|
| GO term | meiotic DNA repair synthesis |
| Ontology | biological_process |
| Synonym | none |
| Definition | During meiosis, the synthesis of DNA proceeding from the broken 3-prime single-strand DNA end that uses the homologous intact duplex as the template. |
| Major function | Repair synthesis coupled to meiotic recombination that helps complete crossover and noncrossover formation. |
| Related processes | Meiotic double-strand break repair, homologous recombination, DNA strand invasion, and DNA synthesis tract formation. |
| Key regulators | Dna2, SYCP2, BCAS2, hnRNPH1, Mre11-Rad50-Nbs1 and Tel1/ATM influence related repair and recombination steps. |
| Experimental readouts | Genome-wide mapping of repair DNA synthesis tracts and analysis of recombination intermediates. |
What Is GO:0000711?
In this article, meiotic DNA repair synthesis (GO:0000711) refers to the DNA synthesis reaction that starts at a broken 3-prime single-strand DNA end and copies information from an intact homologous duplex during meiosis. It is distinct from general DNA replication because the template is the homologous chromosome rather than a sister chromatid in S phase, and it is coupled to the recombination pathway that processes meiotic double-strand breaks. The process is part of the broader DNA repair and recombination network that includes strand invasion, DNA synthesis, and resolution of recombination intermediates.
Why Is meiotic DNA repair synthesis Important in Cell Biology?
Meiotic DNA repair synthesis is important because it is the DNA-copying step that helps convert a broken meiotic chromosome into a repaired, recombined product, and it is mechanistically coupled to both crossover and noncrossover formation. Without controlled repair synthesis, recombination intermediates may be misprocessed, leading to genome instability or failed meiosis. Because the process uses the homologous intact duplex as a template, it also directly influences how genetic information is exchanged between homologous chromosomes. Understanding this step is therefore relevant to fertility, germ cell development, and the basic mechanisms of homologous recombination.
• It completes the DNA synthesis step of meiotic recombination after strand invasion, enabling crossover and noncrossover formation.
• It uses the homologous intact duplex as a template, which is central to faithful repair during meiosis.
• It is coupled to the processing of programmed meiotic double-strand breaks.
• Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis, linking synthesis to genome stability.
• Proteins such as SYCP2, BCAS2 and hnRNPH1 influence DNA repair and synapsis in meiotic prophase I.
• The Mre11-Rad50-Nbs1 complex and Tel1/ATM kinase control meiotic DNA break formation and repair coordination.
• Genome-wide mapping of repair synthesis tracts provides a quantitative way to study the process in plants such as Arabidopsis thaliana.
• Defects in meiotic recombination and repair synthesis are relevant to infertility and developmental disorders.
• Biochemical studies of genetic recombination and DNA repair provide a mechanistic framework for understanding this synthesis step.
• Translesion synthesis and related repair pathways in germ cells highlight the broader importance of DNA synthesis during germline development.
What Happens During meiotic DNA repair synthesis?
Initiation from a broken 3-prime single-strand DNA end
In simple terms: The process starts at a broken DNA end that has a free 3-prime tip.
Meiotic DNA repair synthesis begins from a broken 3-prime single-strand DNA end, which serves as the primer for DNA synthesis during meiosis. This end is generated as part of the processing of programmed meiotic double-strand breaks, and it is the substrate that allows repair synthesis to proceed using the homologous intact duplex as a template. The formation and processing of these breaks are coordinated with the Mre11-Rad50-Nbs1 complex and Tel1/ATM kinase, which control break formation and repair signaling.
Strand invasion and template use
In simple terms: The broken end invades the intact homologous DNA and uses it as a copy template.
After strand invasion, the broken 3-prime end pairs with the homologous intact duplex, and DNA synthesis copies information from that template. This template-dependent synthesis is a defining feature of GO:0000711 and distinguishes it from other repair synthesis reactions that may use a sister chromatid or a different template. Recombination-coupled DNA synthesis facilitates post-invasion steps in meiotic crossover and noncrossover formations, meaning that the synthesis step is directly linked to the outcomes of recombination.
Repair DNA synthesis tract formation
In simple terms: The new DNA made during repair forms a tract that can be measured.
The DNA synthesized during meiotic repair forms tracts that can be mapped genome-wide, as demonstrated in Arabidopsis thaliana. These repair DNA synthesis tracts provide a quantitative readout of where synthesis occurred and how far it extended, linking the molecular step to chromosomal outcomes. The formation of these tracts is coupled to the recombination machinery that processes double-strand breaks and resolves recombination intermediates.
Removal of toxic ssDNA-RPA filaments
In simple terms: A protein called Dna2 cleans up harmful DNA-protein filaments that form during synthesis.
Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis, which helps prevent genome instability during meiosis. This function links the synthesis step to the quality-control machinery that monitors single-stranded DNA and RPA-coated intermediates. Without such removal, recombination-associated synthesis could lead to harmful intermediates that impair meiotic progression.
Coordination with synapsis and prophase I
In simple terms: Repair synthesis happens alongside the pairing of chromosomes in early meiosis.
Meiotic DNA repair synthesis occurs in the context of meiotic prophase I, where synapsis and recombination are coordinated. BCAS2 and hnRNPH1 orchestrate alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I, indicating that splicing regulation supports the repair process. SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair, further linking meiotic chromosome structures to repair outcomes.
Key Genes Involved in GO:0000711 meiotic DNA repair synthesis
The following genes and proteins have been experimentally linked to meiotic DNA repair synthesis or closely related meiotic recombination and repair steps.
| Gene | Major Role | Research Relevance |
|---|---|---|
| Dna2 | Removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis | Studying genome stability during meiotic synthesis |
| SYCP2 | Confers resistance to DNA-damaging agents through R-loop-mediated DNA repair | Linking synaptonemal complex proteins to repair |
| BCAS2 | Orchestrates alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I | Splicing regulation in meiotic repair |
| hnRNPH1 | Orchestrates alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I | RNA-binding protein function in meiosis |
| Mre11 | Part of the Mre11-Rad50-Nbs1 complex controlling meiotic DNA break formation and repair | Break formation and repair signaling |
| Rad50 | Part of the Mre11-Rad50-Nbs1 complex controlling meiotic DNA break formation and repair | Break formation and repair signaling |
| Nbs1 | Part of the Mre11-Rad50-Nbs1 complex controlling meiotic DNA break formation and repair | Break formation and repair signaling |
| Tel1/ATM | Protein kinase that mutually controls meiotic DNA break formation with Mre11-Rad50-Nbs1 | ATM signaling in meiosis |
| RPA | Forms ssDNA-RPA filaments that are removed by Dna2 during meiotic recombination-associated DNA synthesis | Single-strand DNA handling |
| Arabidopsis recombination machinery | Produces measurable meiotic double-strand break repair DNA synthesis tracts | Plant model for genome-wide tract mapping |
| Recombination-coupled DNA synthesis factors | Facilitate post-invasion steps in meiotic crossover and noncrossover formations | Mechanistic studies of crossover and noncrossover |
| Translesion synthesis factors | Required for primordial germ cell DNA demethylation and development | Germ cell development and DNA synthesis |
| Biochemical recombination factors | Mechanistic components of genetic recombination and DNA repair | In vitro reconstitution and biochemistry |
How Is meiotic DNA repair synthesis Regulated?
Meiotic DNA repair synthesis is regulated by the interplay between break-forming and break-repair machinery. The Mre11-Rad50-Nbs1 complex and Tel1/ATM kinase exert mutual, spatially limited control of meiotic DNA break formation, which in turn influences when and where repair synthesis can occur. Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis, providing a quality-control layer that prevents harmful intermediates. Alternative splicing factors such as BCAS2 and hnRNPH1 regulate DNA double-strand break repair and synapsis in meiotic prophase I, indicating that RNA processing contributes to the regulation of this process. SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair, linking chromosome structure and R-loop biology to repair regulation.
meiotic DNA repair synthesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SYCP2 | DNA damage resistance and R-loop-mediated repair | Knockout or overexpression cell models to test DNA damage sensitivity |
| BCAS2 | Meiotic prophase I DNA repair and synapsis | Knockout models to assess splicing and repair defects |
| hnRNPH1 | Meiotic prophase I DNA repair and synapsis | Knockout or point-mutation models to study splicing regulation |
| Dna2 | Genome instability from ssDNA-RPA filaments | Knockout or tagged knock-in models to track filament removal |
| Mre11/Rad50/Nbs1 | Meiotic DNA break formation and repair signaling | Point-mutation or knockout models to dissect break control |
Meiotic repair synthesis and infertility
Defects in meiotic recombination and repair can impair germ cell development and fertility, and proteins such as SYCP2, BCAS2 and hnRNPH1 have been linked to DNA repair and synapsis in meiotic prophase I. Because meiotic DNA repair synthesis is required for completing recombination, failures in this step may contribute to meiotic arrest or germ cell loss. Studying these mechanisms in model systems can help identify causes of infertility related to meiotic recombination defects.
Genome instability and cancer biology
Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis, and failure of this quality-control step can lead to genome instability. SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair, connecting meiotic chromosome proteins to cellular responses to DNA damage. These findings suggest that mechanisms related to meiotic repair synthesis may inform our understanding of genome maintenance more broadly.
Germ cell development and translesion synthesis
Primordial germ cell DNA demethylation and development require DNA translesion synthesis, highlighting the importance of specialized DNA synthesis pathways in germ cells. Although translesion synthesis is distinct from meiotic DNA repair synthesis, both illustrate how DNA synthesis steps are essential for germline development. Understanding these pathways may help explain how germ cells balance repair, synthesis and epigenetic reprogramming.
From meiotic DNA repair synthesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does a candidate gene affect meiotic DNA repair synthesis? | Knockout cell model with a repair synthesis reporter |
| Does a specific amino acid change alter repair synthesis? | Point-mutation knock-in model |
| Where and when is a repair protein localized during meiosis? | Tagged knock-in model for imaging |
| Does overexpression of a repair factor change synthesis tracts? | Overexpression cell model |
| How does loss of Dna2 affect ssDNA-RPA filaments? | Knockout or point-mutation model |
| How does splicing regulation influence meiotic repair? | Knockout or knockdown of BCAS2/hnRNPH1 |
How to Study the meiotic DNA repair synthesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Genome-wide repair synthesis tract mapping | Locations and extent of meiotic DNA repair synthesis | Comparing wild-type and mutant meiosis |
| Biochemical reconstitution | Enzymatic steps of recombination and repair | Defining minimal factors for synthesis |
| Crossover/noncrossover assays | Post-invasion outcomes of recombination | Testing whether synthesis is required for crossover or noncrossover |
| ssDNA-RPA filament analysis | Toxic intermediates generated during synthesis | Assessing Dna2 function |
| DNA damage sensitivity assays | Cellular resistance to DNA-damaging agents | Testing SYCP2 function |
| Splicing analysis | Alternative splicing of repair genes | Studying BCAS2 and hnRNPH1 |
| Break formation mapping | Meiotic DNA break positions | Analyzing Mre11-Rad50-Nbs1 and Tel1/ATM control |
| Translesion synthesis assays | DNA synthesis across lesions in germ cells | Studying primordial germ cell development |
Genome-wide mapping of repair DNA synthesis tracts
Meiotic double-strand break repair DNA synthesis tracts can be mapped genome-wide, as shown in Arabidopsis thaliana, providing a direct readout of where synthesis occurred. This approach allows researchers to quantify the distribution and extent of repair synthesis across the genome. It is particularly useful for comparing wild-type and mutant conditions that affect recombination.
Biochemical reconstitution of recombination and repair
Biochemical mechanisms of genetic recombination and DNA repair can be studied through reconstitution and enzymatic assays. Such approaches help define the minimal factors required for repair synthesis and the order of reactions. They complement genetic and cell-based studies by providing mechanistic detail.
Analysis of recombination intermediates and products
Recombination-coupled DNA synthesis facilitates post-invasion steps in meiotic crossover and noncrossover formations, so assays that measure crossover and noncrossover products are informative. These assays can reveal whether synthesis is required for one or both outcomes. They are often combined with mutants that affect repair synthesis to test causality.
Imaging and protein localization in meiotic prophase I
Tagged knock-in models can be used to visualize repair proteins during meiotic prophase I. Such imaging helps determine whether a protein localizes to sites of recombination and whether its localization depends on repair synthesis. These studies are often paired with DNA damage sensitivity assays.
How CRISPR Can Be Used to Study GO:0000711 meiotic DNA repair synthesis
Knockout
CRISPR knockout models can be used to remove candidate genes involved in meiotic DNA repair synthesis and test whether repair synthesis tracts or recombination outcomes are affected. For example, knocking out Dna2 can reveal its role in removing toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis. Knockout of splicing factors such as BCAS2 or hnRNPH1 can test their requirement for DNA double-strand break repair and synapsis in meiotic prophase I.
Point Mutation
Point-mutation knock-in models allow precise testing of amino acid residues required for repair synthesis or its regulation. For instance, mutations in Mre11-Rad50-Nbs1 or Tel1/ATM can be introduced to dissect their mutual control of meiotic DNA break formation and repair. Such models help distinguish catalytic functions from scaffolding or signaling roles.
Knock-in
Tagged knock-in models enable visualization and biochemical isolation of proteins involved in meiotic DNA repair synthesis. For example, tagging SYCP2 or BCAS2 can reveal their localization during meiotic prophase I and their association with repair sites. Knock-in of reporter cassettes can also provide a direct readout of repair synthesis at defined loci.
Overexpression
Overexpression models can test whether increased levels of a repair factor alter the extent or distribution of meiotic DNA repair synthesis. Overexpressing Dna2, for example, may affect the removal of ssDNA-RPA filaments and influence genome stability. Overexpression of splicing factors such as BCAS2 or hnRNPH1 can reveal dose-dependent effects on repair and synapsis.
How EDITGENE Supports meiotic DNA repair synthesis Research
Researchers studying meiotic DNA repair synthesis-related genes often need to determine whether a candidate gene is causally involved in the synthesis step, how specific mutations affect its function, and where the protein acts during meiosis. EDITGENE provides CRISPR-based cell models and screening services that enable such causal tests in relevant cell backgrounds.
Contact EDITGENE today to design your custom CRISPR model for meiotic DNA repair synthesis research.
Frequently Asked Questions About meiotic DNA repair synthesis
What is meiotic DNA repair synthesis?
Meiotic DNA repair synthesis (GO:0000711) is the synthesis of DNA from a broken 3-prime single-strand DNA end using the homologous intact duplex as the template during meiosis.
What genes are involved in meiotic DNA repair synthesis?
Genes and proteins linked to this process or closely related steps include Dna2, SYCP2, BCAS2, hnRNPH1, Mre11, Rad50, Nbs1 and Tel1/ATM.
Why is meiotic DNA repair synthesis important?
It helps complete recombination by facilitating post-invasion steps in crossover and noncrossover formation and supports genome stability during meiosis.
How is meiotic DNA repair synthesis measured?
It can be measured by genome-wide mapping of repair DNA synthesis tracts, as shown in Arabidopsis thaliana, and by assays of recombination intermediates.
What does Dna2 do in meiotic DNA repair synthesis?
Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis.
How do Mre11-Rad50-Nbs1 and Tel1/ATM regulate meiotic DNA breaks?
They exert mutual, spatially limited control of meiotic DNA break formation, which influences when repair synthesis can occur.
What is the role of SYCP2 in DNA repair?
SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair.
How do BCAS2 and hnRNPH1 affect meiosis?
They orchestrate alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I.
Can CRISPR be used to study meiotic DNA repair synthesis?
Yes, CRISPR knockout, point-mutation, knock-in and overexpression models can be used to test gene function in this process.
Is meiotic DNA repair synthesis related to human disease?
Defects in meiotic recombination and repair are relevant to infertility and genome instability, and proteins such as SYCP2 and Dna2 have been linked to DNA repair and stability.
Conclusion
Meiotic DNA repair synthesis (GO:0000711) is the template-directed DNA synthesis step that uses a broken 3-prime single-strand end and the homologous intact duplex to complete meiotic recombination. It is coupled to post-invasion steps in crossover and noncrossover formation and is safeguarded by factors such as Dna2 that remove toxic ssDNA-RPA filaments. Key proteins including SYCP2, BCAS2, hnRNPH1, Mre11-Rad50-Nbs1 and Tel1/ATM influence related repair, synapsis and break formation, making this process a rich area for mechanistic and disease-relevant research. CRISPR-based knockout, point-mutation, knock-in, overexpression and screening models provide practical tools to dissect these mechanisms in relevant cell systems.
References
- 1. Hernández Sánchez-Rebato M et al.. 2024. Meiotic double-strand break repair DNA synthesis tracts in Arabidopsis thaliana.. PLoS Genet 20(7):e1011197 PMID: 39012914
- 2. Raina VB et al.. 2025. Biochemical Mechanisms of Genetic Recombination and DNA Repair.. Annu Rev Biochem 94(1):161-193 PMID: 40153609
- 3. Wang Y et al.. 2024. Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair.. Nat Commun 15(1):1568 PMID: 38383600
- 4. Choi H et al.. 2025. Recombination-coupled DNA synthesis facilitates post-invasion steps in meiotic crossover and noncrossover formations.. Nucleic Acids Res 53(14) PMID: 40716778
- 5. Sun L et al.. 2024. BCAS2 and hnRNPH1 orchestrate alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I.. Cell Mol Life Sci 81(1):449 PMID: 39520542
- 6. Zhai B et al.. 2023. Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis.. Nucleic Acids Res 51(15):7914-7935 PMID: 37351599
- 7. Shah P et al.. 2024. Primordial germ cell DNA demethylation and development require DNA translesion synthesis.. Nat Commun 15(1):3734 PMID: 38702312
- 8. Hyppa RW et al.. 2025. Mutual, spatially limited control of meiotic DNA break formation by Mre11-Rad50-Nbs1 DNA repair complex and Tel1 (ATM) protein kinase.. Nucleic Acids Res 53(22) PMID: 41428730
