Urinary cPU concentrations were quantified with liquid chromatography–tandem mass spectrometry, while expression of six nucleotide excision repair genes—XPB, XPC, XPD, XPF, ERCC1 and CSB—was measured in peripheral blood samples using quantitative reverse transcription PCR. The investigators described the study as an assessment of DNA-lesion levels and repair-gene expression in people with bipolar disorder, their unaffected siblings and healthy controls. The cPUs examined are tandem oxidative lesions that distort the DNA helix and impair replication and transcription.

The source study states that they are repaired primarily by the nucleotide excision repair pathway. Both the bipolar disorder and sibling groups had significantly elevated urinary cPU concentrations compared with healthy controls. R-cdA concentrations were highest in the sibling group.

These observations show that elevated lesion concentrations were present in the two groups sharing a family connection, rather than only among participants diagnosed with bipolar disorder. The group comparison did not establish whether the concentrations preceded illness, caused bipolar disorder or predicted future symptoms. Expression of four repair-related genes was increased in the sibling group: XPB, XPF, ERCC1 and CSB.

XPC expression was elevated in both the bipolar disorder and sibling groups relative to healthy controls. Other comparisons distinguished the sibling group from the bipolar disorder group. XPB, XPF and CSB expression was significantly higher in siblings than in participants with bipolar disorder, whereas XPD expression was increased in the bipolar disorder group compared with both the sibling and healthy-control groups.

The results therefore comprised elevated cPU concentrations in both family-linked groups and distinct patterns of repair-gene expression among bipolar disorder participants, unaffected siblings and controls. The authors interpreted the combined findings as support for prior evidence implicating oxidative DNA damage and repair mechanisms in bipolar disorder pathogenesis. They proposed that the cPU lesions and the differing expression patterns may be useful as additional molecular markers and may indicate a potential familial vulnerability associated with the development of bipolar disorder.

The study itself does not demonstrate that elevated lesions or altered gene expression cause the disorder, that either precedes its onset, or that either constitutes a clinical diagnostic test. The results instead identify measurable molecular differences in bipolar disorder and unaffected sibling groups that warrant further investigation as potential indicators of oxidative DNA damage and altered repair activity.

Subject of Research: Oxidative DNA lesions and nucleotide excision repair gene expression in bipolar disorder, unaffected siblings and healthy controls

Article Title: Cyclopurine DNA lesions and repair in individuals with bipolar disorder and their unaffected siblings

Article References: Arat Çelik, H. E., Tuna, G., Akşahin, İ. C., Yılmaz, S., Fettahoğlu, İ., Eslami Abriz, A., Gör, C., Çörekli, E., Kök Kendirlioğlu, B., Dal Bekar, N. E., Çelik, Ö. F., Yorguner, N., & Ceylan, D. (2026). Cyclopurine DNA lesions and repair in individuals with bipolar disorder and their unaffected siblings. Translational Psychiatry. https://doi.org/10.1038/s41398-026-04519-z

Image Credits: AI Generated

DOI: 10.1038/s41398-026-04519-z

Keywords: bipolar disorder, oxidative DNA lesions, nucleotide excision repair, DNA repair, familial vulnerability, gene expression, R-cdA, mass spectrometry, peripheral blood, biomarkers, Cyclopurine, lesions

The clinical burden of xeroderma pigmentosum extends well beyond what is visible on the skin surface. Because the nucleotide excision repair pathway normally removes a wide range of bulky DNA lesions, patients with defects in this pathway accumulate damage not only from ultraviolet radiation but also from certain environmental mutagens encountered in daily life. The consequence is a progressive disease course in which early pigmentary changes give way to actinic damage, premalignant lesions, and invasive cancers at rates far exceeding those seen in the general population. Understanding why patients in complementation group A experience such a severe phenotype requires examining how the XPA protein coordinates the individual steps of the repair reaction, from damage recognition through dual incision and gap filling.

Nucleotide excision repair is mechanistically distinctive among DNA repair pathways because it does not recognize a single type of chemical lesion. Instead, it detects distortions in the DNA helix produced by diverse adducts, including the cyclobutane pyrimidine dimers and 6-4 photoproducts generated by ultraviolet light. This versatility comes at a cost: the pathway requires a large multiprotein assembly that must be recruited sequentially to the damage site, verified, and then handed off to the enzymatic components that carry out the incision steps. XPA, although it lacks catalytic activity of its own, sits at the center of this assembly process. It interacts with multiple NER factors and helps verify that a genuine lesion is present before the costly incision and resynthesis steps are undertaken. This checkpoint-like function means that even subtle defects in XPA can propagate through the entire pathway, impairing steps far downstream of the initial recognition event.

The distinction between processive and distributive mechanisms of action is central to understanding how repair proteins search for and act upon lesions embedded in chromatin. A distributive enzyme dissociates from DNA after each catalytic event and must rebind independently to find the next site, a strategy that becomes increasingly inefficient as the search space grows. A processive enzyme, by contrast, remains associated with its substrate through multiple consecutive events, sliding or stepping along the DNA molecule. In the crowded environment of the nucleus, where DNA is wrapped around histone octamers and folded into higher-order structures, the advantage of a processive search mechanism is substantial. A protein that can remain tethered to DNA while traversing nucleosome-bound regions has a far greater probability of encountering a lesion before dissociating than one that must repeatedly diffuse through three-dimensional space and rebind.

The proposal that XPA functions as a processivity factor for the endonucleases XPF and XPG reframes how these enzymes can be understood in the context of NER. XPF, in complex with ERCC1, carries out the 5′ incision, while XPG performs the 3′ incision that releases the damaged oligonucleotide. Both enzymes must locate the precise phosphodiester bonds flanking the lesion, positions that are determined by the geometry of the repair bubble rather than by the lesion itself. If these endonucleases operate distributively, as appears to be the case in XP-A cells, each incision event requires an independent encounter with the damaged site, and the efficiency of the dual incision reaction drops markedly. The observation that recombinant normal human XPA can correct this defect in XP-A cell extracts demonstrates that the processivity defect is directly attributable to the absence of functional XPA rather than to secondary changes that accumulate in these cells.

The structural basis for XPA’s role in processivity likely resides in its DNA binding domain, which spans multiple exons of the gene. Mutations in exons 3 and 5 that abolish XPA’s ability to enhance endonuclease processivity point to specific regions of the protein that are required for this function. The exon 5 mutation, identified in two patients with severe clinical presentations, provides a direct link between a defined molecular defect and the severity of disease. This kind of genotype-functional phenotype correlation is valuable because it moves beyond simply cataloging mutations and instead explains why particular amino acid changes produce particular clinical outcomes. It also suggests that the DNA binding domain of XPA is not merely a passive anchor but an active participant in coordinating the movement of repair enzymes along damaged DNA.

The challenge posed by nucleosomal DNA deserves particular attention. In vivo, approximately three-quarters of genomic DNA is packaged into nucleosomes at any given time, and the wrapping of DNA around the histone core restricts access by repair proteins. Lesions on the outward-facing surface of the nucleosome are more accessible than those facing the histone octamer, creating positional effects on repair efficiency. Chromatin-remodeling complexes can partially alleviate this barrier by repositioning or restructuring nucleosomes near damage sites, but the endonucleases themselves must still be able to function on DNA that is only transiently exposed. A processive mechanism of action may be especially advantageous in this context because it allows an enzyme to remain engaged with a stretch of chromatinized DNA long enough to complete incisions even when nucleosome repositioning is incomplete. The reduced incision of damaged nucleosomal DNA observed in XP-A cells is consistent with this interpretation and suggests that loss of XPA-mediated processivity compounds the inherent difficulty of repairing DNA in chromatin.

The involvement of the XPB/TFIIH translocase adds another dimension to the processivity model. TFIIH contains the XPB ATPase-translocase, which unwinds DNA around the lesion to generate the open bubble structure required for incision. Studies of XPA from the thermophilic fungus Chaetomium thermophilus indicate that XPA can increase the processivity of this translocase as it moves along UV-damaged DNA. The conservation of this function across eukaryotic evolution suggests that XPA’s role as a processivity factor is a fundamental feature of the NER pathway rather than a mammalian-specific adaptation. It also implies that the coordination between damage verification, bubble opening, and incision may depend on XPA’s ability to keep multiple enzymatic components engaged with the DNA substrate simultaneously.

From a therapeutic standpoint, the identification of specific molecular defects that correlate with clinical severity opens several possible avenues. If the loss of processivity in XP-A cells can be attributed to defined structural features of the mutant XPA protein, it may be possible to design small molecules or peptide mimetics that restore the missing function. Alternatively, gene therapy approaches aimed at delivering a functional copy of the XPA gene to affected tissues could, in principle, restore normal processivity to the endonucleases and improve repair of nucleosomal DNA. Even partial restoration of function might produce meaningful clinical benefit, given that the relationship between residual repair capacity and disease severity is not strictly linear. The development of such approaches will require continued effort to map the functional domains of XPA and to understand how each domain contributes to the overall coordination of the NER reaction in the context of chromatinized DNA.

The broader significance of these findings extends beyond XP-A. Other complementation groups involve proteins that also participate in the sequential assembly of the NER machinery, and defects in any of these components could similarly affect the processivity of downstream enzymes. Understanding how XPA confers processivity on XPF, XPG, and XPB/TFIIH may therefore illuminate general principles of how multi-protein repair complexes achieve efficiency on substrates that are chemically diverse and structurally occluded by chromatin. Such principles could be relevant to other DNA repair pathways that must operate on nucleosomal templates, and to the design of interventions that enhance repair capacity in contexts where it is compromised, whether through inherited mutation, age-related decline, or environmental exposure.

Subject of Research: XPA confers ability of endonucleases to act processively and to incise damaged nucleosomal DNA

Article Title: XPA confers ability of endonucleases to act processively and to incise damaged nucleosomal DNA

Article References: Lambert, M. W., & Lambert, W. C. (2026). XPA confers ability of endonucleases to act processively and to incise damaged nucleosomal DNA. Experimental Biology and Medicine, 251, Article 10902. https://doi.org/10.3389/ebm.2026.10902

Image Credits: AI Generated

DOI: 10.3389/ebm.2026.10902

Keywords: confers, ability, endonucleases, processively, incise, damaged, nucleosomal, scientific research

Fluoroquinolones, which include widely used drugs such as ciprofloxacin and levofloxacin, kill bacteria by trapping DNA gyrase and topoisomerase IV on the chromosome, converting these essential enzymes into agents of DNA destruction. The resulting double-strand breaks and associated lesions are lethal to most cells. But in stationary-phase cultures, where nutrients are scarce and most bacteria have stopped dividing, persisters survive fluoroquinolone treatment at high frequency. Previous work from the same research group demonstrated something surprising: transient growth inhibition after the antibiotic was removed significantly increased the recovery of persisters from stationary-phase Escherichia coli populations, but only if two specific genes were intact. One was recA, the central mediator of homologous recombination, and the other was uvrD, a DNA helicase that functions in nucleotide excision repair. That finding suggested that persister recovery depends on coordinated action between two repair systems that biologists usually study in isolation.

To dissect this relationship, the team turned to epistasis analysis, a classical genetic approach in which researchers construct double mutants and compare their behavior to that of the corresponding single mutants. If two genes operate in the same pathway, deleting both typically produces no worse a defect than deleting either one alone. If they operate in parallel, compensatory, or synergistic pathways, the double mutant reveals a different phenotype. By deleting DNA repair enzymes known to physically or functionally interact with RecA or UvrD, and then measuring how the resulting mutant strains recovered from fluoroquinolone treatment, the researchers could chart the boundaries of the persister recovery network with unprecedented resolution.

The results confirmed that the network extends well beyond the two original genes. Within nucleotide excision repair, the excision nuclease components uvrA and uvrB, along with mfd, a transcription-repair coupling factor that directs repair machinery to RNA polymerase-stalled sites, were all found to epistatically interact with recA during persister recovery. On the homologous recombination side, recB and recC, which encode the subunits of the RecBCD nuclease-helicase complex that processes DNA ends for recombination, emerged as additional epistatic partners of uvrD. These findings establish that both pathways genuinely contribute to the recovery phenomenon rather than serving as incidental bystanders, and they suggest that fluoroquinolone-induced damage in persisters generates substrates that require both excision of bulky lesions and recombinational repair of strand breaks.

Yet the data also revealed that the network is more nuanced than a simple story of one pathway compensating for the loss of the other. Loss of recA had far-reaching epistatic consequences that were not mirrored by the loss of other homologous recombination genes, indicating that RecA performs functions in persister recovery that its pathway partners do not fully duplicate. Similarly, loss of uvrD had a greater impact on the network than the loss of any other nucleotide excision repair gene tested. This asymmetry is significant because it implies that RecA and UvrD are not interchangeable cogs in a repair pipeline but rather hub proteins whose specific biochemical activities are indispensable for the recovery program. The double-mutant combinations across the two pathways produced patterns that could not be explained by straightforward redundancy, hinting at regulatory or structural roles that go beyond canonical repair chemistry.

To test whether the canonical enzymatic functions of these two hub proteins were actually required, the researchers deployed separation-of-function mutants. RecA(N304D) is a variant that retains some activities of the protein but is specifically defective in its recombination function, while UvrD(R284A) carries a mutation that abolishes its ATP-dependent helicase activity. If persister recovery depended merely on the physical presence of these proteins, for example as DNA-binding scaffolds, these mutants should have supported recovery. They did not. The recombination-proficient form of RecA and the helicase-active form of UvrD were both strictly required for their participation in fluoroquinolone persister recovery. This result anchors the phenomenon in biochemistry: the actual motor and strand-exchange activities of these enzymes, not just their occupancy of the DNA, drive the repair that allows persisters to resume growth after antibiotic treatment ends.

The findings carry weight for a long-standing debate in the microbiology of antibiotic tolerance. For years, persisters were assumed to survive because their sluggish metabolism rendered them invisible to antibiotics. Fluoroquinolones complicate that picture, because these drugs can form lesions even in metabolically quiescent cells, and the new work reinforces the view that survival after fluoroquinolone exposure is an active, repair-dependent process. In other words, persisters are not merely hiding from the drug; they are fighting back with the same DNA repair arsenal that dividing cells use, albeit under conditions of transient growth arrest that appear to give the repair machinery time to work. The post-treatment growth inhibition that boosts recovery in the laboratory may mimic conditions persisters encounter in infected tissues, where nutrient limitation and immune pressures can stall bacterial growth after antibiotic levels decline.

There are also therapeutic implications worth considering. If RecA and UvrD sit at the center of the persister recovery network, they become attractive targets for adjunctive drugs designed to sensitize persisters. Inhibitors that compromise RecA-mediated recombination or UvrD helicase activity could, in principle, be paired with fluoroquinolones to prevent the repair that underpins survival, thereby reducing the reservoir of tolerant cells that can seed recurrent infections. The epistasis map constructed in this study provides a rational starting point for such efforts, because it identifies which combinations of repair functions must be blocked to collapse the network. The asymmetry in the data suggests that targeting the hubs, RecA and UvrD, might be more effective than targeting peripheral components such as UvrA, UvrB, Mfd, RecB, or RecC.

Caveats remain, as they always do in laboratory genetics. The study was conducted in Escherichia coli grown to stationary phase in culture, and persister physiology in vivo, within the context of an actual infection, may involve additional stress responses, host factors, and heterogeneous metabolic states that alter the repair network’s composition. Moreover, epistasis analysis reveals functional relationships but does not by itself identify the molecular substrates being repaired or the sequence in which the pathways act. Future work combining the genetic framework established here with direct measurements of DNA damage, repair kinetics, and single-cell recovery dynamics will be needed to convert the network map into a mechanistic model.

Even so, the study represents a substantial advance in understanding how bacteria survive one of medicine’s most important antibiotic classes. By systematically expanding the persister recovery network and demonstrating that the core enzymatic activities of RecA and UvrD are non-negotiable requirements, Soto-Echevarria, Lemma, and Brynildsen have transformed a curious observation about post-treatment growth arrest into a genetically grounded framework. The work deepens appreciation of the interplay between homologous recombination and nucleotide excision repair in non-dividing cells, and it sharpenens the rationale for attacking persister survival at its enzymatic roots. As antibiotic resistance continues to erode treatment options worldwide, strategies that target tolerance rather than resistance are gaining urgency, and this study offers a detailed molecular blueprint for where such strategies might strike.

Subject of Research: Epistatic interactions between nucleotide excision repair and homologous recombination in fluoroquinolone persister recovery in Escherichia coli

Article Title: Genetic analysis of epistasis between nucleotide excision repair and homologous recombination in the recovery of persisters after fluoroquinolone treatment

Article References: Soto-Echevarria, N., Lemma, A. S., & Brynildsen, M. P. (2026). Genetic analysis of epistasis between nucleotide excision repair and homologous recombination in the recovery of persisters after fluoroquinolone treatment. PLOS Genetics, 22(9), e1012305. https://doi.org/10.1371/journal.pgen.1012305

Image Credits: AI Generated

DOI: 10.1371/journal.pgen.1012305

Keywords: antibiotic persisters, fluoroquinolones, DNA repair, RecA, UvrD, homologous recombination, nucleotide excision repair, epistasis, Escherichia coli, antibiotic tolerance, stationary phase, PLOS Genetics

Now, a comprehensive critical review published in Molecular Biology Reports by Tianshun Xu, Yaoyang Shen, and colleagues at Ningbo University’s Health Science Center has taken stock of the entire toolbox that scientists use to measure how well human cells perform this vital repair job. The review, led by corresponding authors Geng Wang and Na Li, systematically compares the biochemical, cellular, and genome-wide methods currently available for functional NER analysis, examining what each technique actually measures, how it works, and where its blind spots lie. In doing so, it offers researchers a kind of field guide to an area of biology that has grown fragmented across decades of methodological innovation, and it arrives at a deceptively simple conclusion: no single assay tells the whole story.

To appreciate why measuring NER is so tricky, it helps to understand what the pathway actually does. NER operates through two intertwined branches. Global-genome NER, abbreviated GG-NER, patrols the entire genome, scanning for distortions caused by lesions such as the cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidinone photoproducts generated by ultraviolet light. In this surveillance mode, the XPC-RAD23B complex, often assisted by the UV-damaged DNA-binding protein complex, serves as the primary damage sensor. The second branch, transcription-coupled NER, is triggered when RNA polymerase II stalls at a lesion blocking its progress along a gene. Stalled transcription is itself the alarm bell, recruiting factors such as CSB, CSA, and UVSSA that hand the problem over to the shared repair machinery. Both branches converge on a common core: the transcription factor IIH, with its XPB and XPD helicase subunits, verifies the damage and opens the DNA, XPA and RPA help position the incision nucleases XPF-ERCC1 and XPG, and the damaged stretch is cut out as a short oligonucleotide roughly 24 to 32 nucleotides long. The resulting gap is filled by repair synthesis and sealed by ligation.

Because the pathway unfolds in discrete stages, from damage recognition through dual incision, gap filling, and ligation, different assays capture different snapshots of the process. The Ningbo review organizes the field around exactly this principle, grouping methods by the endpoint they interrogate: excision-product formation, repair-associated DNA synthesis, transcriptional or reporter gene-expression recovery, lesion removal inferred from restored DNA amplifiability, and genome-wide mapping of damage and excision events. Each category carries its own technical logic, its own strengths, and its own interpretive caveats, and the review’s central message is that assay selection must be guided by the specific research question at hand, with complementary readouts providing the most complete picture of NER function.

At the biochemical end of the spectrum sit the in vitro excision assays, which trace their lineage to the pioneering work of Aziz Sancar’s laboratory and others who reconstituted human NER in cell-free extracts in the late 1980s and early 1990s. In these systems, damaged plasmid DNA is incubated with cell extracts or purified protein fractions, and the dual-incision products, the small excised oligonucleotides carrying the lesion, are detected by gel electrophoresis or immunological methods. The approach offers exquisite mechanistic resolution: researchers can pinpoint exactly which protein factors are required for each step, as demonstrated in landmark studies that defined the minimal set of human factors needed to reconstitute dual incision. Recent structural biology has pushed this mechanistic understanding even further, with cryo-electron microscopy revealing the pre-incision complexes and the scanning-to-incision switch in TFIIH-XPG that licenses repair. Yet the review is careful to note the limitations of cell-free systems. Extract-based assays strip away the chromatin context in which repair actually occurs in living cells, and studies going back decades have shown that NER is suppressed in reconstituted nucleosomes, meaning that what works beautifully in a test tube may not reflect the chromatin-wrapped reality of the nucleus.

Moving into living cells, the review highlights the classic unscheduled DNA synthesis assay, a technique with roots stretching back to 1964, when Rasmussen and Painter first reported evidence of DNA repair in cultured mammalian cells. Because repair synthesis inserts new nucleotides outside the normal S phase of the cell cycle, it was dubbed unscheduled, and measuring this incorporation, originally with radioactive thymidine and later with the click-chemistry-compatible analog EdU, became the gold-standard functional readout of global-genome NER for decades. The assay remains clinically relevant: it has been used for prenatal diagnosis of xeroderma pigmentosum, the devastating hereditary disorder in which NER defects cause extreme sun sensitivity and a thousands-fold elevated skin cancer risk, and for complementation analysis of patient cells. Modern refinements, including tyramide signal amplification, have made the assay non-radioactive and sensitive enough for single-cell quantification, and parallel measurements of recovery of RNA synthesis provide the complementary readout for transcription-coupled repair, which is the branch specifically defective in Cockayne syndrome and UV-sensitive syndrome.

Perhaps the most versatile family of cellular assays is host cell reactivation, or HCR, in which a reporter plasmid is deliberately damaged in vitro, for example by UV irradiation or treatment with the cigarette-smoke carcinogen benzo[a]pyrene diol epoxide, and then transfected into the cells under study. If the cells’ NER machinery repairs the plasmid, the reporter gene, historically chloramphenicol acetyltransferase and now typically luciferase or fluorescent proteins, switches back on, and the level of expression becomes a proxy for repair capacity. The elegance of the method lies in its scalability and its epidemiological reach: modified HCR assays have been used to measure DNA repair capacity in peripheral blood lymphocytes from large cohorts, revealing associations between reduced repair capacity and elevated risk of skin, lung, head and neck, and bladder cancers. The latest evolution, fluorescence multiplexed HCR, or FM-HCR, deploys barcoded reporter plasmids carrying different types of damage, each tagged with a distinct fluorescent protein, allowing simultaneous quantification of repair across multiple lesion types and multiple pathways in a single sample by flow cytometry. Recent large-scale applications have measured inter-individual variation in DNA repair capacity across healthy populations, opening the door to personalized assessments of genome maintenance.

The most technologically ambitious methods in the review are the genome-wide approaches, chief among them excision repair sequencing, or XR-seq, developed in Sancar’s laboratory. Rather than measuring repair indirectly, XR-seq captures the actual excised oligonucleotides that NER releases, maps them back to the reference genome by next-generation sequencing, and thereby produces single-nucleotide-resolution maps of where repair happened across the entire genome. The technique has generated striking biological insights: repair is faster in transcribed genes than in silent regions, it is modulated by chromatin state, it follows circadian rhythms in mouse tissues, and it varies systematically across the three-dimensional organization of the genome, as shown in recent work mapping the repair of aflatoxin-induced and cisplatin-induced damage. Complementary damage-mapping methods such as Damage-seq and high-sensitivity variants locate the lesions themselves, so that comparing damage maps with excision maps reveals repair kinetics directly. These approaches have even been extended beyond humans, illuminating repair patterns in plants, yeast, and bacteria, and connecting transcription-coupled repair to the Mfd translocase in E. coli.

Why does all this methodological scrutiny matter beyond the laboratory? The review emphasizes that NER sits at a fascinating double-edged intersection with cancer. On one hand, robust NER protects normal cells from mutagenesis, and epidemiological studies have linked weaker repair phenotypes to higher cancer risk. On the other hand, cancer cells can co-opt elevated NER activity to survive the DNA-damaging chemotherapy drugs that oncologists deploy against them. Cisplatin adducts and other bulky lesions are themselves NER substrates, so tumors with high repair capacity can shrug off treatment. This has fueled a therapeutic strategy of NER inhibition: the review’s authors themselves have previously shown that triptolide, a natural product, enhances carboplatin-induced apoptosis in melanoma by suppressing NER activity. Accurate, well-matched assays are therefore essential not only for understanding basic biology but also for identifying which tumors might respond to such combination therapies and for monitoring how interventions actually change repair function in cells.

The review’s final verdict is a call for methodological humility and deliberate design. Because each assay interrogates a distinct stage or consequence of NER, a positive result in one assay cannot be automatically generalized to the whole pathway, and apparent discrepancies between studies may simply reflect different endpoints rather than conflicting biology. Biochemical assays offer mechanistic precision but lack cellular context; cellular reporter assays capture functional outcomes but can be influenced by transcription, replication, and toxicity; genome-wide maps deliver unprecedented resolution but demand substantial sequencing resources and computational expertise. The authors argue that researchers should choose their tools to match their questions and, wherever possible, layer complementary readouts, for example pairing an excision assay with a repair-synthesis measurement or a genome-wide map with a functional reporter, to build a comprehensive assessment of NER capability. As DNA repair biology moves from correlation toward causation in cancer prevention, diagnosis, and treatment, that disciplined, multi-angle approach may prove to be the review’s most enduring contribution.

Subject of Research: Functional methods for assessing nucleotide excision repair capability in human cells

Article Title: Assessment and detection of nucleotide excision repair capability in human cells: a critical review of current functional methods

Article References: Xu, T., Shen, Y., Dai, X., Shao, Y., Zhang, Y., Zhang, Y., Wang, G., & Li, N. (2026). Assessment and detection of nucleotide excision repair capability in human cells: a critical review of current functional methods. Molecular Biology Reports, 53(1), Article 1635. https://doi.org/10.1007/s11033-026-12816-5

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12816-5

Keywords: nucleotide excision repair, DNA damage, DNA repair assays, host cell reactivation, unscheduled DNA synthesis, XR-seq, xeroderma pigmentosum, transcription-coupled repair, genome stability, cancer therapy resistance, TFIIH, functional genomics