# Homologous Recombination: DNA Repair and Genetic Diversity

Every cell in your body faces a constant barrage of DNA damage. Ultraviolet light, reactive oxygen species from metabolism, and errors during [DNA replication](/blog/guides/dna-replication) collectively create thousands of lesions per cell per day. Most are minor and easily repaired, but the most dangerous type—a double-strand break (DSB), where both strands of the DNA helix are severed—threatens chromosome integrity. Left unrepaired, a single DSB can trigger cell death or unleash the genomic chaos that drives cancer.

Cells have evolved two principal strategies to deal with DSBs: non-homologous end joining (NHEJ), which simply re-ligates the broken ends, and homologous recombination (HR), a more elaborate pathway that uses an undamaged copy of the genetic information as a template. HR is the only repair mechanism that can restore the original DNA sequence with absolute fidelity. It is also the engine of genetic diversity in sexually reproducing organisms, shuffling maternal and paternal chromosomes during meiosis. This article explains the molecular mechanics of HR, the proteins that execute it, and why its failure has profound consequences for human health.

## What Is Homologous Recombination?

Homologous recombination is a conserved molecular pathway that exchanges genetic information between two DNA molecules that share extensive sequence similarity. The term "homologous" refers to the requirement that the two DNA molecules must be nearly identical in sequence—typically hundreds of base pairs of uninterrupted match—for the reaction to proceed. This sequence homology provides the information needed to repair a damaged chromosome accurately.

The core of HR is a physical exchange of strands between two DNA duplexes. A single-stranded DNA molecule invades a homologous double-stranded DNA molecule, displacing one of its strands and forming a three-stranded structure. This strand invasion event creates a branched DNA intermediate called a Holliday junction, named after Robin Holliday who proposed the structure in 1964. The Holliday junction is a cross-shaped structure where four DNA strands are held together by base pairing, and it can be resolved by specific enzymes to produce either non-crossover or crossover products.

### Key terms: homology, strand exchange, Holliday junction

**Homology** in this context means sequence identity. For HR to work, the invading single strand must find a region of double-stranded DNA with complementary sequence. In practice, the minimal efficient processing segment (MEPS) in human cells is roughly 200–300 base pairs, though shorter stretches can support recombination at lower efficiency. This requirement ensures that recombination occurs between matching chromosomes or sister chromatids, not between unrelated genomic regions.

**Strand exchange** is the central reaction of HR. It involves the unwinding of the donor duplex, base pairing of the invading strand with its complementary strand, and displacement of the original partner strand. This reaction is catalyzed by recombinase enzymes that polymerize on single-stranded DNA to form a nucleoprotein filament.

**Holliday junctions** are the physical connection between two recombining DNA molecules. A single Holliday junction can form when one end of a DSB invades; two junctions form when both ends participate in the reaction. The resolution of these junctions—by cutting and rejoining the strands—determines whether the recombination event results in a crossover (exchange of flanking markers) or a non-crossover (simple gene conversion without flanking exchange).

## Why Cells Need Homologous Recombination

HR serves two fundamentally different but equally essential functions in biology: the accurate repair of DSBs and the generation of genetic diversity during meiosis. Both roles exploit the same basic chemistry—the use of a homologous template to guide DNA synthesis—but the outcomes are tailored to the cellular context.

### Repair of DNA double-strand breaks

A DSB is a catastrophic lesion. Both strands of the DNA duplex are broken, and the two ends can physically separate. If the cell attempts to rejoin them by NHEJ, it risks introducing small insertions or deletions at the break site because the ends are often damaged and cannot be perfectly ligated. HR offers a superior solution: it uses the intact sister chromatid (in mitotic cells) or the homologous chromosome (in meiotic cells) as a template to copy the missing information.

HR is particularly important during the S and G2 phases of the cell cycle, when a sister chromatid is available. The sister chromatid is an identical copy of the broken chromosome, produced during [DNA replication](/blog/guides/dna-replication), and therefore provides a perfect template. By using this template, HR can restore the original sequence without any loss of information. This is why HR is described as an "error-free" repair pathway, in contrast to the inherently mutagenic NHEJ.

Beyond repairing DSBs, HR also rescues stalled or collapsed replication forks. When a replication fork encounters a lesion in the template strand, it can stall. If the fork collapses—that is, if the replisome disassembles and the fork reverses or breaks—HR can restart replication by invading the intact sister duplex. This function is critical for genome stability, as [replication fork collapse](/knowledge/molecular-biology/replication-fork-collapse) is a major source of spontaneous DSBs in dividing cells.

### Meiotic crossover and genetic variation

In meiosis, HR is deliberately programmed to create crossovers between homologous chromosomes. During prophase I, each chromosome pair undergoes at least one programmed DSB, introduced by the enzyme Spo11. These breaks are repaired by HR using the homologous chromosome as a template, rather than the sister chromatid. The resulting crossover physically connects the homologous chromosomes, ensuring their correct segregation at the first meiotic division.

The crossover also exchanges genetic material between the maternal and paternal chromosomes, creating new combinations of alleles. This process, known as meiotic recombination, is a major source of genetic variation. The number and distribution of crossovers are tightly regulated: each chromosome pair must receive at least one crossover (to ensure proper segregation), but excessive crossovers can cause chromosomal abnormalities. In humans, the average number of crossovers per meiosis is approximately 50–60, distributed across the 23 chromosome pairs.

## The Steps of Homologous Recombination

HR proceeds through a series of ordered steps, each catalyzed by specific proteins. The pathway can be divided into five stages: break recognition, end resection, filament formation, strand invasion, and resolution. The following description focuses on the DSB repair model in eukaryotic cells, with reference to the bacterial system where relevant.

### Double-strand break recognition

The first step is detection of the DSB. In eukaryotic cells, the MRN complex (Mre11-Rad50-Nbs1) is the primary sensor. Mre11 possesses both endonuclease and 3′→5′ exonuclease activities, Rad50 is an ATPase that binds and tethers DNA ends, and Nbs1 recruits additional factors. The MRN complex binds to the broken ends and activates the kinase ATM (ataxia-telangiectasia mutated), which phosphorylates numerous downstream targets, including the histone H2AX. Phosphorylated H2AX (γ-H2AX) spreads over megabase distances flanking the break, serving as a scaffold for the recruitment of repair proteins.

In bacteria, the equivalent sensor is the RecBCD complex, a helicase-nuclease that binds to DSB ends and unwinds the DNA while degrading both strands. When RecBCD encounters a specific sequence element called Chi (5′-GCTGGTGG-3′), its nuclease activity is modified to produce a 3′ single-stranded overhang, which is then loaded with the [RecA recombinase](/knowledge/bioinformatics/genes/microbiology-amr/reca-gene-structure-function-pathway).

### End resection and Rad51 filament formation

For HR to proceed, the broken ends must be converted into 3′ single-stranded DNA (ssDNA) overhangs. This process, called end resection, involves the nucleolytic degradation of the 5′ strands at both ends of the break. In eukaryotes, resection is a two-step process. The MRN complex, together with the protein CtIP, initiates short-range resection, removing approximately 100–300 nucleotides. Long-range resection is then carried out by the exonuclease Exo1 or the helicase-nuclease complex BLM-DNA2, extending the single-stranded overhangs over thousands of base pairs.

The resulting 3′ ssDNA is immediately coated by the heterotrimeric complex RPA (replication protein A). RPA binds ssDNA with high affinity, protecting it from nucleases and removing secondary structure. However, RPA must be displaced for recombination to proceed. This is achieved by the recombinase Rad51, which polymerizes on the ssDNA to form a right-handed helical filament, with approximately 6.5 Rad51 monomers per turn and 3 nucleotides per monomer. The Rad51-ssDNA filament is the catalytic machine that performs strand exchange.

The loading of Rad51 onto ssDNA requires mediator proteins. In yeast, the mediator is Rad52; in humans, the critical mediators are BRCA2 and the Rad51 paralogs (Rad51B, Rad51C, Rad51D, XRCC2, XRCC3). BRCA2 binds directly to Rad51 and facilitates the displacement of RPA, while the paralogs stabilize the filament and promote its assembly.

### Strand invasion and D-loop

The Rad51-ssDNA filament searches the genome for homologous double-stranded DNA. This search is a dynamic process involving transient, non-specific contacts with duplex DNA, followed by sampling for sequence complementarity. When homology is found, the filament invades the duplex, base-pairing the ssDNA with its complementary strand and displacing the original partner strand. The displaced strand forms a single-stranded loop, giving this structure its name: the displacement loop, or D-loop.

The invading 3′ end of the ssDNA is now positioned at the start of a region of homologous duplex. This 3′ end serves as a primer for DNA synthesis. DNA polymerase δ, together with its processivity factor PCNA, extends the invading strand, copying information from the homologous template. The D-loop expands as synthesis proceeds.

In the classical DSB repair model, the second end of the break is then captured. The displaced strand of the D-loop base-pairs with the resected ssDNA on the other side of the break, annealing the two ends. DNA synthesis fills in the remaining gaps, and ligation seals the nicks. This produces a double Holliday junction, connecting the two recombining molecules.

### DNA synthesis and resolution

The double Holliday junction must be resolved to separate the two DNA molecules. Two classes of enzymes catalyze this reaction. Structure-selective nucleases, such as GEN1 and the MUS81-EME1 complex, cut the junctions by symmetrically cleaving two strands at each junction. Depending on which strands are cut, resolution can produce either crossover or non-crossover products.

Alternatively, the double Holliday junction can be dissolved by the BLM-topoisomerase IIIα-RMI1/RMI2 complex. This helicase-topoisomerase complex migrates the two junctions toward each other and then decatenates the resulting hemicatenane, always producing non-crossover products. The choice between resolution and dissolution is regulated by the cell cycle and by post-translational modifications, but the molecular details of this regulation remain an active area of research.

An alternative HR pathway, called synthesis-dependent strand annealing (SDSA), avoids Holliday junction formation altogether. In SDSA, the invading strand is extended by DNA synthesis and then displaced from the D-loop. The extended single strand anneals with the resected ssDNA on the other side of the break, and gap filling completes the repair. SDSA always produces non-crossover products and is the predominant pathway for DSB repair in mitotic cells.

## Key Proteins and Enzymes

HR is executed by a conserved set of proteins, many of which are named for their roles in bacterial recombination or for the human diseases caused by their mutation. The following table summarizes the major players and their functions.

| Protein | Organism | Role in HR |
|---|---|---|
| RecA | Bacteria | Recombinase; forms filament on ssDNA, catalyzes strand exchange |
| RecBCD | Bacteria | Helicase-nuclease; processes DSB ends, loads RecA |
| Rad51 | Eukaryotes | Recombinase; functional homolog of RecA |
| Rad52 | Yeast | Mediator; loads Rad51 onto RPA-coated ssDNA |
| BRCA2 | Humans | Mediator; loads Rad51, displaces RPA |
| Rad51 paralogs | Humans | Stabilize Rad51 filament |
| MRN complex | Eukaryotes | DSB sensor; initiates resection; activates ATM |
| Exo1, DNA2 | Eukaryotes | Long-range resection |
| RPA | Eukaryotes | ssDNA binding protein; protects resected ends |
| BLM | Humans | Helicase; dissolution of double Holliday junctions |
| GEN1, MUS81-EME1 | Humans | Structure-selective nucleases; Holliday junction resolution |

### Rad51/RecA recombinase

The recombinase is the heart of HR. RecA in bacteria and Rad51 in eukaryotes share a conserved ATPase domain and a common mechanism of action. The recombinase binds to ssDNA cooperatively, forming a helical filament with a defined polarity. ATP binding induces a conformational change that stretches the DNA within the filament, making it more accessible for base pairing with a homologous duplex. ATP hydrolysis is not required for strand exchange itself but is needed for the dissociation of the recombinase from the heteroduplex DNA after the reaction, allowing the filament to turn over.

The Rad51 filament is a dynamic structure. It can assemble and disassemble rapidly, and its stability is modulated by accessory factors. In human cells, Rad51 is present at low levels in the nucleus, but upon DNA damage, it accumulates in foci at sites of repair. These foci can be visualized by [immunofluorescence microscopy](/blog/guides/immunofluorescence-microscopy-controls-for-specific-and-reproducible-images) and serve as a readout of HR activity.

### BRCA1 and BRCA2 in human cells

The breast cancer susceptibility proteins BRCA1 and BRCA2 are intimately connected to HR. BRCA2 is the primary mediator for Rad51 loading in human cells. It binds to Rad51 through eight conserved BRC repeat motifs and delivers Rad51 to the site of resection, where it displaces RPA from ssDNA. BRCA2 also stabilizes the Rad51 filament and protects it from dissociation.

BRCA1 has a more complex role. It functions as a scaffold that coordinates multiple steps of the [DNA damage response](/knowledge/molecular-biology/dna-damage-response). BRCA1 is required for the recruitment of resection factors (CtIP, Exo1, DNA2) to the break site, and it also promotes the choice between HR and NHEJ by opposing the NHEJ factor 53BP1. In addition, BRCA1 participates in the activation of the G2/M cell cycle checkpoint, giving the cell time to complete repair before entering mitosis.

Mutations in BRCA1 or BRCA2 predispose to breast, ovarian, prostate, and pancreatic cancers. The tumors that arise from these mutations typically show loss of the wild-type allele, leaving the cell with no functional copy of the gene. These HR-deficient cells are exquisitely sensitive to agents that cause DSBs, a vulnerability that is exploited therapeutically (see below).

## Homologous Recombination vs. Non-Homologous End Joining

Cells face a choice when repairing a DSB: use HR or NHEJ. The decision is governed by the cell cycle phase, the availability of a homologous template, and the structure of the broken ends. The two pathways have fundamentally different outcomes and trade-offs.

| Feature | Homologous Recombination | Non-Homologous End Joining |
|---|---|---|
| Template required | Yes (sister chromatid or homolog) | No |
| Cell cycle | S and G2 phases | All phases, especially G1 |
| Accuracy | Error-free (sequence restored) | Error-prone (small indels common) |
| Speed | Slow (hours) | Fast (minutes) |
| End processing | Extensive resection (5′→3′) | Minimal (end trimming only) |
| Key proteins | Rad51, BRCA2, MRN, Exo1 | Ku70/Ku80, DNA-PKcs, Ligase IV |
| Outcome | Crossover or non-crossover | Direct ligation |

### Error-free vs. error-prone repair

The fundamental trade-off is between accuracy and speed. NHEJ is fast and can operate at any point in the cell cycle, but it often leaves a scar: small insertions or deletions at the break site. These mutations are usually harmless if they occur in non-coding regions, but they can be deleterious if they disrupt a gene. NHEJ is the dominant repair pathway in G1 phase, when no sister chromatid is available for HR.

HR is slower and restricted to S/G2, but it restores the original sequence perfectly. The requirement for a homologous template means that HR is only possible when an undamaged copy of the broken region exists. In diploid cells, the homologous chromosome can serve as a template, but using it risks loss of heterozygosity if the recombination event is resolved as a crossover. For this reason, mitotic cells preferentially use the sister chromatid, which is identical to the broken chromosome.

The choice between HR and NHEJ is regulated by the resection step. If resection occurs, the broken ends are committed to HR; if not, NHEJ proceeds. The tumor suppressor p53-binding protein 1 (53BP1) promotes NHEJ by protecting DNA ends from resection, while BRCA1 counteracts 53BP1 to allow resection and HR. This antagonism is a key determinant of repair pathway choice. For more detail on the NHEJ pathway, see the article on [Non Homologous End Joining Repair](/knowledge/molecular-biology/non-homologous-end-joining-repair).

## Studying Homologous Recombination

HR has been studied for over half a century, and the experimental toolkit for analyzing it is sophisticated. The field has benefited enormously from the genetic tractability of yeast, the development of fluorescent reporter systems, and advances in live-cell microscopy.

### Reporter systems

Fluorescent reporter assays allow researchers to measure HR efficiency in living cells. The most widely used system is the DR-GFP (direct repeat-green fluorescent protein) reporter. This construct contains two copies of the GFP gene arranged as direct repeats: one copy is mutated to contain an I-SceI endonuclease cleavage site, and the other is a truncated, non-functional version. When the I-SceI enzyme is expressed, it creates a DSB at the cleavage site. If the break is repaired by HR using the truncated copy as a template, the GFP gene is restored to full length, and the cell becomes fluorescent. The fraction of fluorescent cells, measured by flow cytometry, provides a quantitative readout of HR efficiency.

Variants of this system use different fluorescent proteins or different arrangements of the repeats to measure specific HR sub-pathways, such as SDSA versus Holliday junction resolution. These reporters have been used to screen for genes involved in HR, to test the effects of mutations in HR factors, and to measure the impact of small-molecule inhibitors.

### Live-cell imaging

The visualization of HR in real time has been made possible by tagging repair proteins with fluorescent proteins. Rad51-GFP fusions form distinct foci at sites of DSBs, and the kinetics of focus formation and disappearance can be followed by time-lapse microscopy. More sophisticated approaches use laser micro-irradiation to create DSBs in a defined region of the nucleus, allowing the recruitment of repair proteins to be monitored with millisecond temporal resolution.

Single-molecule techniques have revealed the dynamics of Rad51 filament assembly and disassembly. Total internal reflection fluorescence (TIRF) microscopy can visualize individual Rad51 filaments on DNA curtains, providing measurements of filament growth rates, nucleation frequencies, and the effects of regulatory proteins. These studies have shown that Rad51 filament assembly is highly dynamic, with continuous association and dissociation of subunits, and that the filament is in a constant state of flux.

## Homologous Recombination in Human Health

The clinical importance of HR is most dramatically illustrated by the link between HR defects and cancer. Inherited mutations in BRCA1 or BRCA2 confer a lifetime risk of breast cancer of 60–80% and ovarian cancer of 20–50%, among other cancers. The tumors that arise in these patients are characterized by genomic instability, including chromosomal rearrangements and copy number alterations, reflecting the failure of HR to maintain genome integrity.

### BRCA mutations and cancer risk

Why do BRCA mutations specifically predispose to breast and ovarian cancer, rather than cancer in all tissues? The answer is likely related to the high proliferative rate of breast and ovarian epithelium and the exposure of these tissues to estrogen, which can cause DNA damage through its metabolites. Cells in these tissues experience frequent replication stress, and the loss of HR makes them unable to cope with the resulting DSBs. The accumulation of mutations and chromosomal aberrations drives tumorigenesis.

The tumors that arise in BRCA mutation carriers typically show loss of heterozygosity at the BRCA locus, meaning that the wild-type allele has been lost and no functional BRCA protein remains. This is consistent with the "two-hit" model of [tumor suppressor genes](/knowledge/molecular-biology/tumor-suppressor-gene), where both alleles must be inactivated for tumor formation.

### PARP inhibitors and synthetic lethality

The discovery that HR-deficient cells are exquisitely sensitive to PARP inhibitors has revolutionized the treatment of BRCA-mutant cancers. PARP (poly(ADP-ribose) polymerase) is an enzyme that binds to single-strand breaks and facilitates their repair by the [base excision repair](/knowledge/molecular-biology/base-excision-repair) pathway. When PARP is inhibited, single-strand breaks persist and are converted to DSBs during DNA replication. In normal cells, these DSBs are repaired by HR. In BRCA-deficient cells, HR is non-functional, and the DSBs are either repaired by error-prone NHEJ or left unrepaired, leading to cell death.

This phenomenon is called synthetic lethality: the combination of two non-lethal defects (PARP inhibition and HR deficiency) is lethal, while each defect alone is tolerated. PARP inhibitors such as olaparib and niraparib are now standard therapies for BRCA-mutant ovarian and breast cancers. The success of this approach has spurred efforts to identify other genetic contexts that confer PARP inhibitor sensitivity, a concept known as "BRCAness."

## Common Misconceptions and Pitfalls

Several misconceptions about HR are common among students encountering the topic for the first time. Clarifying these points is essential for a correct understanding.

### HR vs. crossing over

HR is often equated with crossing over, but the two are not synonymous. Crossing over refers specifically to the reciprocal exchange of flanking markers that occurs when a Holliday junction is resolved in the crossover configuration. HR can also produce non-crossover products, where genetic information is transferred without exchange of flanking markers. In mitotic cells, non-crossover products predominate, and crossing over is suppressed because it can lead to loss of heterozygosity. In meiosis, crossing over is required for proper chromosome segregation, but even in meiosis, the majority of recombination events are non-crossovers.

The distinction matters for understanding the outcomes of HR. A non-crossover event can convert a small region of sequence (gene conversion) without altering the arrangement of genes on the chromosome. A crossover event, by contrast, swaps entire chromosome arms. The two outcomes have very different genetic consequences.

### Template requirement

HR requires a homologous template. This is a non-negotiable requirement: without a template, HR cannot proceed. The template can be a sister chromatid, a homologous chromosome, or even an ectopic sequence located elsewhere in the genome. The requirement for homology is what distinguishes HR from NHEJ, which can join any two DNA ends regardless of sequence.

The template requirement has practical implications. In haploid cells, such as yeast in the G1 phase of the cell cycle, HR is essentially impossible because no homologous template exists. Similarly, in human cells in G1, HR is suppressed because the sister chromatid has not yet been synthesized. The cell cycle dependence of HR is a direct consequence of the template requirement.

Another common misconception is that HR is involved in the pairing of homologous chromosomes during meiosis. While HR does occur between homologous chromosomes during meiosis, the initial pairing of homologs is a separate process mediated by the synaptonemal complex and other proteins. The relationship between pairing and recombination is complex: recombination is required for stable pairing in most organisms, but the initial recognition of homology occurs through a different mechanism. For a discussion of the distinction, see the article on [No Recombination of Homologs](/knowledge/molecular-biology/no-recombination-of-homologs).

## Summary and Key Takeaways

Homologous recombination is a fundamental DNA repair pathway that uses sequence homology to restore broken chromosomes with high fidelity. It is essential for repairing double-strand breaks, restarting stalled replication forks, and generating genetic diversity during meiosis. The pathway is executed by a conserved set of proteins, with the recombinase Rad51 (or RecA in bacteria) at its core. Defects in HR, particularly in BRCA1 and BRCA2, predispose to cancer, and the synthetic lethality of HR deficiency with PARP inhibition has become a cornerstone of targeted cancer therapy.

## Frequently Asked Questions

### What is homologous recombination?

Homologous recombination is a process of exchanging genetic information between two DNA molecules that share similar sequences. It is used by cells to repair double-strand breaks in DNA and to generate genetic diversity during meiosis.

### What are the steps of homologous recombination?

The main steps are: (1) recognition of the double-strand break, (2) end resection to create 3′ single-stranded overhangs, (3) assembly of the Rad51 filament on the single-stranded DNA, (4) strand invasion into a homologous duplex to form a D-loop, (5) DNA synthesis using the homologous template, and (6) resolution of the recombination intermediates.

### What is homologous recombination used for?

Homologous recombination is used for three main purposes: repairing double-strand breaks in DNA, restarting stalled or collapsed replication forks, and generating genetic diversity during meiosis by creating crossovers between homologous chromosomes.

### Can you give an example of homologous recombination?

During meiosis in humans, each chromosome pair undergoes programmed double-strand breaks that are repaired by homologous recombination using the homologous chromosome as a template. This creates crossovers that are visible as chiasmata and are required for proper chromosome segregation.

### What is a simple definition of homologous recombination?

Homologous recombination is a DNA repair mechanism that uses an undamaged, similar DNA sequence as a template to accurately repair a broken chromosome.

### How does homologous recombination differ from non-homologous end joining?

Homologous recombination requires a homologous template and is error-free, but it is slow and only works in the S and G2 phases of the cell cycle. Non-homologous end joining does not require a template, is fast, and works in all cell cycle phases, but it often introduces small insertions or deletions at the break site. See the [Non Homologous End Joining Pathway](/knowledge/molecular-biology/non-homologous-end-joining-pathway) for more details.

### What is the role of Rad51 in homologous recombination?

Rad51 is the recombinase enzyme that catalyzes the central reaction of homologous recombination. It forms a filament on single-stranded DNA, searches for homologous double-stranded DNA, and promotes strand invasion to form the D-loop.

## Key Takeaways

- Homologous recombination is an error-free DNA repair pathway that uses a homologous template to restore broken chromosomes.
- The pathway is essential for repairing double-strand breaks, restarting stalled replication forks, and generating genetic diversity during meiosis.
- The core reaction is strand exchange, catalyzed by the Rad51/RecA recombinase, which forms a filament on single-stranded DNA and invades a homologous duplex.
- BRCA1 and BRCA2 are critical human HR factors; their mutation predisposes to breast, ovarian, and other cancers.
- PARP inhibitors exploit the synthetic lethality of HR deficiency, providing a targeted therapy for BRCA-mutant tumors.
- HR differs from NHEJ in its requirement for a template, its cell cycle restriction, and its accuracy.
- The choice between HR and NHEJ is regulated by end resection, which commits the break to HR and is opposed by the NHEJ factor 53BP1.

## Further Reading

- Cejka P, Symington LS. *DNA End Resection: Mechanism and Control*. Annual review of genetics. 2021. [PubMed 34813349](https://doi.org/10.1146/annurev-genet-071719-020312)
- San Filippo J, Sung P, Klein H. *Mechanism of eukaryotic homologous recombination*. Annual review of biochemistry. 2008. [PubMed 18275380](https://doi.org/10.1146/annurev.biochem.77.061306.125255)
- Wright WD, Shah SS, Heyer WD. *Homologous recombination and the repair of DNA double-strand breaks*. The Journal of biological chemistry. 2018. [PubMed 29599286](https://doi.org/10.1074/jbc.TM118.000372)
- Doig KD, Fellowes AP, Fox SB. *Homologous Recombination Repair Deficiency: An Overview for Pathologists*. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2023. [PubMed 36788098](https://doi.org/10.1016/j.modpat.2022.100049)
- Dibitetto D, Widmer CA, Rottenberg S. *PARPi, BRCA, and gaps: controversies and future research*. Trends in cancer. 2024. [PubMed 39004561](https://doi.org/10.1016/j.trecan.2024.06.008)
- Konstantinopoulos PA et al. *Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer*. Cancer discovery. 2015. [PubMed 26463832](https://doi.org/10.1158/2159-8290.CD-15-0714)

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* [Nucleotide Formation: Biosynthesis and Assembly of DNA/RNA Building Blocks](/knowledge/molecular-biology/nucleotide-formation)