# recA Recombinase: Homologous Recombination, SOS Stress Response, and DNA Strand Exchange Mechanics


## Key Takeaways

- RecA is a pivotal bacterial DNA-dependent ATPase that forms helical nucleoprotein filaments on single-stranded DNA (ssDNA), catalyzing homologous recombination and acting as a master regulator of the SOS DNA damage response by stimulating LexA repressor cleavage.
- The *recA* gene is often part of a bicistronic operon with *recX*, which encodes a protein that negatively regulates RecA's recombinase and coprotease activities, providing a crucial feedback mechanism to prevent excessive recombination and SOS induction.
- RecA's essential role in DNA repair, natural transformation, and the SOS response directly impacts antibiotic resistance evolution by promoting mutagenesis and facilitating horizontal gene transfer of resistance determinants.
- Loss-of-function mutations in *recA* render bacteria highly sensitive to DNA-damaging agents and impair natural transformation, while constitutive SOS mutants exhibit hyper-recombination, highlighting RecA's critical regulatory functions.
- RecA is a significant target for antimicrobial therapy, as its inhibition can potentiate existing antibiotics, prevent resistance development by blocking SOS-induced mutagenesis, and inhibit the spread of resistance genes via horizontal gene transfer.
- Beyond DNA repair, RecA is implicated in bacterial pathogenesis, influencing virulence, biofilm formation, host colonization, and the integration of pathogenicity islands, underscoring its broad impact on bacterial biology and clinical outcomes.

---

## Executive Summary & Key Metadata

The *recA* gene encodes Recombinase A (RecA), a 38-kDa protein that is the central catalyst of homologous recombination (HR) and the master regulator of the SOS DNA damage response in bacteria. RecA is a DNA-dependent ATPase that assembles into a helical nucleoprotein filament on single-stranded DNA (ssDNA), a structure that performs two mechanistically distinct functions: (i) it catalyzes the search for homology and the subsequent strand exchange with a homologous double-stranded DNA (dsDNA) molecule, and (ii) it serves as a coprotease that stimulates the autocatalytic cleavage of the LexA transcriptional repressor, thereby derepressing the SOS regulon. Beyond its role in DNA repair, RecA is a critical determinant of horizontal gene transfer, natural transformation, biofilm formation, and the evolution of antibiotic resistance. The protein is conserved across all domains of life, with eukaryotic orthologs RAD51 and DMC1 performing analogous functions in mitosis and meiosis, respectively [1, 2, 3].

| **Attribute** | **Detail** |
| :--- | :--- |
| **HGNC Symbol** | recA (bacterial gene; no human ortholog under this symbol) |
| **UniProt Accession** | P0A7G6 (*Escherichia coli* RecA) |
| **Representative PDB ID** | 2RE7 (*E. coli* RecA filament) |
| **Chromosomal Locus** | *E. coli* K-12: 2,822,500–2,823,570 bp (MG1655 genome) |
| **Primary Molecular Function** | DNA strand exchange; ATP-dependent homologous recombination; SOS coprotease activity |
| **Disease & Pathology Associations** | Antibiotic resistance evolution; bacterial virulence; biofilm formation; host colonization |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Context in *Escherichia coli*

In the model organism *Escherichia coli* K-12, the *recA* gene is located at approximately 58.2 minutes on the genetic map, corresponding to nucleotide positions 2,822,500 to 2,823,570 on the circular chromosome (GenBank: U00096.2). The gene is transcribed in the clockwise direction and is flanked by the *recX* gene immediately downstream (3' end), with which it shares a complex regulatory and functional relationship [4]. The *recA* promoter region contains two key regulatory elements: a LexA binding site (SOS box) and a cyclic AMP receptor protein (CRP) binding site, reflecting its dual control by DNA damage and catabolite repression.

### 1.2 Promoter Architecture and Transcriptional Regulation

The *recA* promoter (PrecA) is one of the most extensively characterized SOS-regulated promoters. It contains a canonical LexA box with the consensus sequence 5'-CTGTATATATATACAG-3', positioned between the -10 and -35 elements. Under normal growth conditions, LexA binds this operator with high affinity, repressing *recA* transcription. Upon DNA damage, RecA nucleoprotein filaments stimulate LexA autocleavage, leading to derepression and a rapid ~10-fold increase in *recA* mRNA levels within minutes [5, 6]. The CRP binding site permits glucose-sensitive regulation, linking recombination capacity to metabolic state.

### 1.3 Operon Structure and the *recX* Gene

The *recA* gene is the first gene of a bicistronic operon that includes *recX* (also known as *oraA*). The *recX* gene encodes a 17-kDa protein that physically interacts with RecA and modulates its activities. RecX inhibits both the recombinase and coprotease functions of RecA *in vitro* and *in vivo*, acting as a negative regulator that prevents excessive recombination and SOS induction [4]. The co-transcription of *recA* and *recX* ensures that the inhibitor is produced in concert with its target, providing a built-in negative feedback loop.

### 1.4 Isoforms and Post-Transcriptional Processing

In most eubacteria, *recA* is a single-copy gene encoding a single polypeptide of 352 amino acids (in *E. coli*). However, alternative forms exist:

- **Intein-containing RecA**: In *Mycobacterium tuberculosis* and other mycobacteria, the *recA* gene contains an in-frame intervening protein sequence (intein) that must be spliced out post-translationally to produce functional RecA. This intein is conditionally spliced in response to cellular stress, providing an additional layer of regulation [7].
- **Truncated variants**: Cloned truncated *recA* genes have been shown to produce dominant-negative or partially functional proteins, revealing the importance of C-terminal residues for full activity [8].
- **Eukaryotic paralogs**: The eukaryotic RecA homologs RAD51 and DMC1 are encoded by distinct genes but share significant structural and functional homology with bacterial RecA [1, 2, 3].

### 1.5 Genomic Organization in Other Bacteria

The *recA* gene is nearly ubiquitous in bacteria, though its genomic context varies. In *Neisseria gonorrhoeae*, the *recA* gene was cloned and sequenced, revealing a GC content and codon usage adapted to the Neisserial genome [9]. In *Shigella sonnei*, the *recA* gene shows high sequence identity to *E. coli* RecA, consistent with their close phylogenetic relationship [10]. In *Bacillus cereus*, *recA* is essential for root colonization, indicating that its role extends beyond DNA repair to include environmental adaptation [11]. The gene is also used extensively as a phylogenetic marker for bacterial taxonomy, particularly in genera where 16S rRNA analysis provides insufficient resolution [12, 13, 14, 15, 16].

---

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Overall Fold and Domain Organization

The RecA protein from *E. coli* (UniProt: P0A7G6) is a 352-amino-acid polypeptide that folds into a compact structure with two major domains: an N-terminal ATPase domain and a C-terminal domain involved in DNA binding and filament stabilization. The protein assembles into a right-handed helical filament with approximately 6.2 subunits per turn and a pitch of ~95 Å, as revealed by X-ray crystallography of the *E. coli* RecA filament (PDB: 2RE7) [17].

### 2.2 N-Terminal ATPase Domain (Residues 1–240)

The N-terminal domain contains the Walker A motif (P-loop, residues 66–73: GPHGAGKT) and Walker B motif (residues 140–144: DE), which together form the ATP binding pocket. ATP hydrolysis drives the conformational changes required for DNA strand exchange. Key residues include:

- **Lys72** (Walker A): Coordinates the β- and γ-phosphates of ATP; mutation to Arg (K72R) abolishes ATP hydrolysis but retains ATP binding, creating a dominant-negative protein.
- **Asp144** (Walker B): Coordinates Mg²⁺ ion required for catalysis.
- **Glu96**: Catalytic glutamate that activates the water molecule for nucleophilic attack on the γ-phosphate.

### 2.3 DNA Binding Loops (L1 and L2)

Two disordered loops, L1 (residues 157–165) and L2 (residues 195–209), protrude from the core domain and are responsible for binding ssDNA and dsDNA. These loops are highly flexible in the absence of DNA but become ordered upon filament formation. The L2 loop contains conserved aromatic residues (Phe203, Tyr204) that intercalate between DNA bases, unwinding the duplex and extending the DNA to ~1.5× its B-form length [17].

### 2.4 C-Terminal Domain (Residues 241–352)

The C-terminal domain is primarily involved in protein-protein interactions and filament stabilization. It contains:

- **The C-terminal tail (residues 300–352)**: A highly acidic region that modulates DNA binding affinity and is the target of several regulatory proteins, including RecX [4].
- **The monomer-monomer interface**: Residues in this region form salt bridges and hydrophobic contacts that stabilize the helical filament.
- **The LexA coprotease binding site**: A groove on the filament surface that accommodates LexA and other SOS repressors (e.g., UmuD, phage repressors).

### 2.5 Structural Comparison with Eukaryotic Orthologs

The RecA fold is conserved in the eukaryotic RAD51 and DMC1 proteins, which share ~30% sequence identity with bacterial RecA but exhibit nearly identical core structures [1, 2, 3]. RAD51 filaments have a similar helical architecture but a different pitch (~130 Å) and require mediator proteins (e.g., BRCA2 in humans) for assembly on ssDNA [3]. The archaeal RadA protein represents an intermediate form, with biochemical properties more similar to bacterial RecA [18, 19].

### 2.6 Interactive 3D Visualization

[Interactive 3D Protein Visualizer: Load recA (PDB: 2RE7)](/tools/protein-structure-viewer?source=direct&pdbId=2RE7)

This visualizer allows exploration of the RecA filament structure, including the ATP binding pocket, DNA binding loops, and subunit interfaces. Users can rotate the structure, highlight key residues, and overlay sequence conservation data.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The RecA Nucleoprotein Filament: Structure and Assembly

The functional unit of RecA is the nucleoprotein filament, formed by the cooperative polymerization of RecA monomers on ssDNA in the presence of ATP (or ATP-γ-S, a non-hydrolyzable analog). The filament has a right-handed helical structure with a deep groove that accommodates the DNA. Assembly proceeds in the 5'→3' direction, with a nucleation step followed by rapid elongation. The filament can also form on dsDNA, though with lower affinity and different functional consequences [1].

### 3.2 Homologous Recombination and Strand Exchange

The central reaction catalyzed by RecA is the exchange of strands between two homologous DNA molecules. This process proceeds through several distinct steps:

1. **Presynapsis**: RecA polymerizes on ssDNA (produced by resection of double-strand breaks or processing of stalled replication forks) to form the presynaptic filament.
2. **Synapsis**: The filament searches for homologous dsDNA sequences. This search is rapid and involves multiple weak contacts before a stable triple-stranded intermediate is formed.
3. **Strand exchange**: The incoming ssDNA pairs with its complementary strand in the dsDNA, displacing the original partner strand. This reaction proceeds in the 5'→3' direction relative to the ssDNA and requires ATP hydrolysis.
4. **Post-synapsis**: The heteroduplex DNA is released, and the filament disassembles, allowing downstream processing by helicases, nucleases, and polymerases.

The efficiency of strand exchange is modulated by accessory proteins. The RecFOR complex loads RecA onto ssDNA gaps, while RecBCD processes double-strand breaks to generate 3' overhangs that serve as RecA substrates [2]. The RecX protein inhibits RecA activity by promoting filament disassembly, preventing uncontrolled recombination [4].

### 3.3 The SOS Response: RecA as a Coprotease

In addition to its recombinase activity, RecA functions as a coprotease that stimulates the autocatalytic cleavage of the LexA repressor. When RecA forms a filament on ssDNA, it adopts a conformation that binds LexA and stabilizes its autocatalytic cleavage conformation. This cleavage inactivates LexA, leading to the derepression of more than 40 SOS genes, including:

- **DNA repair genes**: *uvrA*, *uvrB*, *uvrD* (nucleotide excision repair); *recN*, *recG*, *ruvA*, *ruvB* (recombination and repair).
- **Error-prone polymerases**: *dinB* (Pol IV), *umuD*, *umuC* (Pol V) [3, 4].
- **Cell division inhibitors**: *sulA*, which prevents septation until DNA damage is repaired.
- **Prophage induction**: RecA stimulates the cleavage of phage repressors (e.g., λ CI), leading to prophage activation [5].

The SOS response is a classic example of a bistable genetic switch, with RecA acting as both the sensor of DNA damage and the effector of the response [5, 6].

### 3.4 RecA in Natural Transformation and Horizontal Gene Transfer

RecA is essential for natural transformation in many bacteria, including *Streptococcus pneumoniae* and *Vibrio cholerae* [6, 7, 8, 9]. During transformation, exogenous DNA is taken up as ssDNA and integrated into the chromosome via RecA-dependent homologous recombination. In *S. pneumoniae*, the RecA-directed recombination pathway initiates at chromosomal replication forks, coupling transformation to DNA replication [6, 7]. This process is critical for the acquisition of antibiotic resistance genes and virulence factors.

### 3.5 RecA in Biofilm Formation and Colonization

RecA has been implicated in biofilm formation and host colonization in several bacterial species. In *Streptococcus mutans*, RecA deficiency results in reduced biofilm formation and altered glucosyltransferase expression [10, 11]. In *Bacillus cereus*, RecA is required for efficient root colonization, suggesting a role in stress resistance and environmental adaptation [11]. These functions are likely mediated through the SOS response and the repair of DNA damage encountered during host-microbe interactions.

### 3.6 Protein-Protein Interaction Network

RecA interacts with a wide range of proteins, as documented in BioGRID and STRING databases. Key interactors include:

- **LexA**: The SOS repressor, cleaved upon RecA filament formation.
- **RecX**: A negative regulator of RecA filament stability [4].
- **RecF, RecO, RecR**: Mediators that load RecA onto ssDNA [2].
- **RecBCD**: A helicase-nuclease that processes dsDNA breaks to generate RecA substrates.
- **UmuD/UmuD'**: Components of Pol V, which interact with RecA during SOS mutagenesis [3].
- **DprA**: A transformation mediator that loads RecA onto incoming ssDNA in *S. pneumoniae* [9].
- **PcrA**: A helicase that disrupts RecA filaments, preventing excessive recombination [12].
- **RadA (archaeal)**: A RecA paralog that enhances ssDNA binding and strand displacement [18].

### 3.7 Regulatory Feedback Loops

RecA activity is subject to multiple layers of regulation:

- **Transcriptional**: LexA represses *recA* transcription; SOS induction relieves this repression [5].
- **Post-translational**: RecX promotes filament disassembly, limiting RecA activity [4].
- **Allosteric**: ATP binding and hydrolysis modulate the conformational state of RecA, affecting its affinity for DNA and coprotease substrates.
- **Competition**: Other DNA-binding proteins (e.g., SSB, PcrA) compete with RecA for ssDNA substrates, influencing filament formation [12].

```mermaid
sequenceDiagram
    participant DSB as "DNA Damage (DSB/SS Gap)"
    participant RecBCD as "RecBCD Complex"
    participant SSB as "SSB Protein"
    participant RecA as "RecA Monomers"
    participant Filament as "RecA-ssDNA Filament"
    participant LexA as "LexA Repressor"
    participant SOS as "SOS Genes (uvrA, dinB, sulA, etc.)"
    participant RecX as "RecX Inhibitor"
    DSB->>RecBCD: Double-strand break recognition
    RecBCD->>SSB: Resection to 3' overhang
    SSB->>RecA: ssDNA coated by SSB
    RecA->>Filament: Polymerization on ssDNA (ATP-dependent)
    Filament->>LexA: Coprotease stimulation
    LexA->>SOS: Autocleavage & derepression
    SOS->>RecA: Increased recA transcription (positive feedback)
    Filament->>RecX: RecX binding
    RecX->>Filament: Filament disassembly (negative feedback)
    Filament->>DSB: Strand exchange with homologous dsDNA
    DSB->>DSB: DNA repair completed
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Mutational Spectrum of *recA*

While *recA* is not a human disease gene, mutations in bacterial *recA* have profound clinical implications, particularly in the context of antibiotic resistance and virulence. The mutational spectrum of *recA* has been extensively characterized in *E. coli* and other pathogens.

### 4.2 Constitutive SOS Mutants (Protease-Constitutive)

Mutations that render RecA constitutively active in its coprotease function (i.e., able to cleave LexA without DNA damage) have been mapped to specific residues. Wang and Tessman identified several such mutants, including:

- **Glu38 → Lys (E38K)**: This mutation enhances RecA's ability to form filaments on dsDNA, leading to constitutive SOS activation even in the absence of DNA damage [1, 13]. The E38K mutant exhibits hyper-recombination activity and is used to study the regulatory mechanisms that normally restrain RecA activity [14, 15].
- **Arg60 → Cys (R60C)**: Another protease-constitutive mutant that bypasses the requirement for ssDNA.
- **Gly204 → Ser (G204S)**: Located in the L2 DNA binding loop, this mutation alters DNA binding specificity and promotes constitutive filament formation.

These mutants have been instrumental in understanding the conformational changes that activate RecA's coprotease function [13].

### 4.3 Loss-of-Function Mutations

Null mutations in *recA* result in a pleiotropic phenotype characterized by:

- **Extreme sensitivity to DNA-damaging agents** (UV, ionizing radiation, mitomycin C).
- **Deficient homologous recombination** (reduced conjugational and transductional recombination).
- **Loss of SOS induction** (no LexA cleavage, no error-prone repair).
- **Impaired natural transformation** in competent species [6, 7].
- **Reduced biofilm formation** in *S. mutans* and other species [11].
- **Impaired colonization** in plant-associated bacteria [11].

The construction of *recA* null mutants has been achieved in numerous species using various strategies, including insertional mutagenesis, PCR-based gene disruption, and recombinase-mediated targeting [1, 2, 3, 16, 17, 18, 19].

### 4.4 Dominant-Negative Mutations

The K72R mutation (Walker A) produces a RecA protein that binds ATP but cannot hydrolyze it. This protein forms stable filaments on ssDNA but is unable to perform strand exchange, acting as a dominant-negative inhibitor of wild-type RecA. This mutant has been used extensively to study the role of ATP hydrolysis in RecA function.

### 4.5 Clinical Implications of *recA* Mutations

In pathogenic bacteria, *recA* mutations have significant clinical consequences:

- **Antibiotic resistance**: RecA-mediated SOS response promotes the mutagenesis that generates antibiotic resistance mutations. Fluoroquinolones, which cause DNA damage, induce the SOS response and increase mutation rates, accelerating resistance development [4, 17].
- **Virulence**: RecA is required for the expression of certain virulence factors and for survival within host cells. In *Actinobacillus actinomycetemcomitans*, a *recA* mutant shows reduced virulence [1].
- **Horizontal gene transfer**: RecA is essential for the integration of horizontally acquired DNA, including pathogenicity islands and antibiotic resistance cassettes [5].
- **Phase variation**: In *Azospirillum lipoferum*, RecA is involved in phase variation, a mechanism that generates phenotypic diversity [2].

### 4.6 RecA as a Target for Antimicrobial Therapy

Given its central role in DNA repair and the SOS response, RecA is an attractive target for antimicrobial therapy. Inhibiting RecA would:

- Sensitize bacteria to DNA-damaging antibiotics.
- Prevent the SOS-induced mutagenesis that drives resistance development.
- Block horizontal gene transfer and the spread of resistance genes.

Several small-molecule inhibitors of RecA have been identified, and nanobodies targeting the LexA-RecA interaction have been developed as a novel suppression strategy for the SOS response [4].

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Bacteriophage Interactions

RecA plays a central role in the life cycle of many bacteriophages, particularly those that integrate into the host chromosome as prophages. The SOS response, triggered by RecA filament formation, leads to the cleavage of phage repressors and the induction of the lytic cycle. This is exemplified by bacteriophage λ, whose CI repressor is cleaved in a RecA-dependent manner [5].

The F55 virus-encoded transcription regulator from *Sulfolobus* spindle-shaped virus 1 (SSV1) interacts with the host RadA recombinase (an archaeal RecA homolog), revealing a conserved strategy for sensing UV-induced DNA damage across Archaea and Bacteria [5]. This interaction suggests that viruses have evolved to exploit the host recombination machinery for their own activation.

### 5.2 Phage-Encoded Recombinases

Bacteriophages encode their own recombinases, many of which are functional analogs of RecA. The UvsX protein of bacteriophage T4 is a RecA-type recombinase that promotes strand exchange and stimulates DNA replication [6]. Other phage-encoded recombinases include Sak, Redβ, Erf, and Sak4, which belong to the single-strand annealing protein (SSAP) family [7, 8]. These proteins can substitute for RecA in certain contexts and have been harnessed for genetic engineering applications (e.g., the Red/ET recombination system) [9, 16, 18].

### 5.3 Bacterial Pathogenesis and Immune Evasion

RecA contributes to bacterial pathogenesis through multiple mechanisms:

- **Survival within host cells**: RecA-mediated DNA repair is essential for survival in the presence of reactive oxygen species (ROS) and reactive nitrogen intermediates (RNI) produced by host immune cells [10, 11].
- **Antigenic variation**: In *Neisseria gonorrhoeae*, RecA is required for the pilin antigenic variation that allows the bacterium to evade the host immune system [9].
- **Biofilm formation**: RecA promotes biofilm formation in *S. mutans* and other oral pathogens, contributing to dental caries and periodontal disease [10, 11].
- **Colonization**: In *Bacillus cereus*, RecA is crucial for root colonization, demonstrating its role in plant-microbe interactions [11].

### 5.4 RecA in the Evolution of Pathogenicity Islands

RecA-mediated homologous recombination is a major driver of the horizontal gene transfer that shapes pathogen genomes. Pathogenicity islands, such as the *Vibrio* pathogenicity island of epidemic *V. cholerae*, are integrated and excised via recombination events that often involve RecA [5]. The RecET recombination system, derived from the Rac prophage, has been widely used for genetic engineering and gene targeting [16, 18].

---

## 6. [Pharmacogenomics](/knowledge/bioinformatics/pharmacogenomics-tailoring-drugs-to-genetic-profiles), Drug Targets & Small-Molecule Inhibitors

### 6.1 RecA as a Drug Target

The central role of RecA in DNA repair, SOS mutagenesis, and horizontal gene transfer makes it an attractive target for antimicrobial therapy. Inhibiting RecA could:

1. **Potentiate existing antibiotics**: DNA-damaging antibiotics (e.g., fluoroquinolones) induce the SOS response, which promotes survival and mutagenesis. RecA inhibitors would block this protective response, increasing antibiotic efficacy [4, 17].
2. **Prevent resistance development**: By blocking SOS-induced mutagenesis, RecA inhibitors would reduce the rate at which bacteria acquire resistance mutations [17].
3. **Block horizontal gene transfer**: RecA inhibitors would prevent the integration of horizontally acquired DNA, limiting the spread of resistance genes.

### 6.2 Small-Molecule Inhibitors of RecA

Several small molecules have been identified as RecA inhibitors:

- **ATP analogs**: Non-hydrolyzable ATP analogs (e.g., ATP-γ-S) block RecA function by preventing ATP hydrolysis.
- **DNA binding inhibitors**: Compounds that compete with DNA for binding to the L1/L2 loops.
- **Filament disruptors**: Compounds that promote filament disassembly or prevent polymerization.

High-throughput screening has identified several lead compounds, though none have yet reached clinical trials.

### 6.3 Nanobody-Based Inhibition of the SOS Response

A novel approach to inhibiting the SOS response involves nanobodies that target LexA autocleavage. These nanobodies bind to LexA and prevent its RecA-mediated cleavage, thereby blocking SOS induction. This strategy has been shown to sensitize bacteria to DNA-damaging antibiotics and reduce the emergence of resistance [4].

### 6.4 RecA in Gene Therapy and Genetic Engineering

RecA and its homologs have been harnessed for various biotechnological applications:

- **Recombinase-mediated gene targeting**: RecA-coated ssDNA oligonucleotides have been used for gene targeting in mouse embryos and other systems [12, 13, 14, 15, 16].
- **Sperm-mediated gene transfer (SMGT)**: RecA has been used to facilitate the transfer of exogenous DNA into sperm cells for transgenesis [1, 17, 18, 19].
- **Recombinase polymerase amplification (RPA)**: RecA-family recombinases are used in isothermal DNA amplification assays, such as the detection of *Borrelia burgdorferi* [2].
- **PCR enhancement**: *Thermus thermophilus* RecA has been shown to enhance PCR amplification of DNA viruses such as Hepatitis B virus (HBV) [3].
- **Minicircle DNA production**: RecA-deficient *E. coli* strains have been engineered for the production of minicircle DNA for gene therapy applications [16].

### 6.5 RecA Inhibitors in Cancer Therapy

While RecA itself is not a human protein, its eukaryotic homolog RAD51 is overexpressed in many cancers and contributes to resistance to DNA-damaging chemotherapies. RAD51 inhibitors are being developed as potential cancer therapeutics, and insights from RecA biochemistry are informing these efforts [4, 5, 17].

---

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Accession/ID** | **Description** |
| :--- | :--- | :--- |
| **NCBI Gene** | 948561 | *E. coli* recA gene |
| **Ensembl Bacteria** | b0001 | *E. coli* K-12 recA |
| **UniProt** | P0A7G6 | RecA protein (*E. coli*) |
| **RCSB PDB** | 2RE7 | *E. coli* RecA filament |
| **Gene Ontology (GO)** | GO:0000150 | Recombinase activity |
| | GO:0003677 | DNA binding |
| | GO:0005524 | ATP binding |
| | GO:0006310 | DNA recombination |
| | GO:0006281 | DNA repair |
| | GO:0009314 | Response to radiation |
| | GO:0043565 | Sequence-specific DNA binding |
| **BioGRID** | 100703 | RecA protein interactions |
| **STRING** | P0A7G6 | RecA interaction network |
| **ClinVar** | N/A | No human clinical variants (bacterial gene) |
| **COG** | COG0468 | RecA/RadA recombinase |
| **InterPro** | IPR013765 | DNA recombination and repair protein RecA |
| **Pfam** | PF00154 | RecA family |

---

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[4] Fyfe, J., & Davies, J. (1990). Nucleotide sequence and expression in *Escherichia coli* of the recA gene of *Neisseria gonorrhoeae*. *Gene*. https://www.semanticscholar.org/paper/78ad808a21acd1cc1dc774a5ac41623379ce295b

[5] Park, Y., Shin, H., & Kim, Y.-C. (1999). Cloning and Nucleotide Sequence of the recA Gene from *Shigella sonnei* KNIH104S Isolated in Korea. *Scientific Publication*. https://www.semanticscholar.org/paper/65db8db9a037d81f329e11324c7f0ffb9aeb0ebd

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[7] Schneider, R. F., Hallstrom, K., DeMott, C., & McDonough, K. (2024). Conditional protein splicing of the *Mycobacterium tuberculosis* RecA intein in its native host. *Scientific Reports*. https://www.semanticscholar.org/paper/7de823e17c090bbeca5c7e2ecea1ce2132143a60

[8] Hofstatter, P., Tice, A. K., Kang, S., Brown, M. W., & Lahr, D. (2016). Evolution of bacterial recombinase A (recA) in eukaryotes explained by addition of genomic data of key microbial lineages. *Proceedings of the Royal Society of London. Biological Sciences*. https://www.semanticscholar.org/paper/aea42e54ccac7c5035402f7c0defdbb24e2ec4d8

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