Ping-Kun Zhou

Cyclic GMP-AMP synthase (cGAS) is a DNA sensor that localizes to both the cytosol and the nucleus, with dynamic nucleocytoplasmic shuttling. In the cytosol, it drives innate immune signaling upon detecting misplaced self-DNA or foreign DNA. In the nucleus, cGAS is normally tethered to chromatin and catalytically silent, but upon genotoxic stress it is reactivated and engages in DNA damage repair.How cGAS temporally coordinates these dual functions during genotoxic stress remains unresolved. In this study, we identified a context-dependent phosphorylation timer in cells with detectable nuclear cGAS that balances cGAS effects on immune signaling and DNA repair. In G1 phase, cGAS is rapidly phosphorylated by DNA-PKcs after irradiation. This modification suppresses cGAS catalytic activity and delays downstream immune signaling without affecting non-homologous end joining (NHEJ) repair, thereby prioritizing DNA repair over immune activation. Subsequent dephosphorylation by PPP1CC, occurring 8–12 h later, releases cGAS from damage sites and reactivates the cGAS–STING pathway.In S phase, phosphorylated cGAS selectively blocks homologous recombination(HR) while preserving NHEJ. This prevents pathway competition and favors rapid and efficient repair.Later, PPP1CC-mediated dephosphorylation inhibits NHEJ, restores HR competence, and reactivates cGAS catalytic activity. These findings reveal a spatiotemporal mechanism that couples DNA repair progression to immune activation, suggesting that the phosphorylation status of cGAS may inform the therapeutic timing of combined radiotherapy and immunotherapy.

Radiation-responsive promoters represent a functionally distinct class of transcriptional regulatory elements that translate genotoxic stress signals into quantifiable gene expression outputs. These promoters occupy a unique mechanistic position within the broader radiation biomarker landscape: rather than directly measuring molecular damage products, they report the cellular interpretation of radiation-induced stress through coordinated gene regulatory networks. This review provides a systematic analysis of five major classes of radiation-responsive promoters—microRNA (miRNA) promoters, tRNA-derived small RNA (tsRNA) promoters, acute-phase protein gene promoters, DNA repair gene promoters, and long non-coding RNA (lncRNA) promoters—with emphasis on their regulatory logic, dose-response characteristics, and current evidence for clinical deployment. We further describe four complementary screening strategies: homology-based conservation analysis, functional genomics and transcriptomics, epigenetic modification profiling, and synthetic biology promoter engineering. Applications spanning biosensor development, biological dosimetry, treatment response prediction, and radiation-guided gene therapy are evaluated within a two-track framework that distinguishes biomarker-oriented applications (Track A) from tool-oriented reporter gene systems (Track B). Critical appraisal of current limitations—including insufficient clinical-grade validation, absence of standardized dose-response curves, and reproducibility deficits—is integrated throughout. Future priorities include multi-center prospective validation studies, FAIR-compliant data infrastructure, AI-driven multi-omics integration, and point-of-care detection platforms. Radiation-responsive promoter biology holds significant potential for advancing precision radiotherapy and nuclear emergency medical response, contingent upon systematic closure of the current evidence gap relative to established gold-standard cytogenetic methods.

Following the publication of the above article, an interested reader drew to the authors' attention that the control GAPDH western blots featured in Fig. 2A on p. 434 and Fig. 3A on p. 435 were strikingly similar, albeit they appeared at different sizes and the experimental contexts of these two figures were different. After having re‑examined the original data for these figures, the authors have realized that the GAPDH western bands for Fig. 2A were inadvertently chosen incorrectly. The revised version of Fig. 2, now showing the correct data for the control western blots in Fig. 2A, is shown below. Note that this error did not have a significant impact either on the results or the conclusions reported in this paper. All the authors agree to the publication of this corrigendum. Furthermore, the authors are grateful to the Editor of Oncology Letters for allowing them the opportunity to publish this corrigendum, and they apologize to the readership for any inconvenience caused. [Oncology Letters 16: 431‑438, 2018; DOI: 10.3892/ol.2018.8619]

A systematic literature review of the PubMed database, filtering for publication dates up to and including October 2025, was conducted to identify relevant studies on glucose metabolism and radiotherapy. Radioresistance poses a major therapeutic challenge, in which tumor-associated glucose metabolic reprogramming, characterized by the Warburg effect, supports cellular energy requirements and contributes to radioresistance by facilitating DNA repair and promoting survival pathways. Targeting pivotal glycolytic enzymes, such as hexokinase (HK) and pyruvate kinase M2 (PKM2), and integrating radiotherapy with metabolic modulators have been shown to improve radiosensitivity. Special emphasis is placed on how these interventions remodel the tumor microenvironment and modulate antitumor immunity—emerging factors that influence therapeutic efficacy. This review highlights mechanistic insights and potential therapeutic targets for the development of effective radiosensitization strategies.

The poly(ADP‐ribose) polymerase (PARP) family consists of 17 members of nicotinamide adenine dinucleotide (NAD⁺)‐dependent enzymes that regulate key biological processes by catalyzing adenosine diphosphate (ADP)‐ribosylation, either poly(ADP‐ribosyl)ation (PARylation) or mono(ADP‐ribosyl)ation (MARylation). These biological processes encompass DNA repair, metabolism, telomere maintenance, and immune responses. Based on structural and functional features, the PARP family is classified into subcategories, such as DNA‐dependent PARPs, Tankyrase, CCCH‐type PARPs, MacroPARPs, and atypical PARPs. These enzymes dynamically maintain genome stability through mechanisms, including base excision repair and homologous recombination, while also regulating telomere dynamics and metabolic pathways. Dysregulation of PARP activity is implicated in the pathogenesis of diverse human diseases. Though PARP inhibitors have gained therapeutic interest in oncology, their wider roles in nononcological conditions, such as neurodegenerative diseases, cardiovascular disorders, and viral infections, remain poorly defined. This review elucidates the unique structural features of PARP family members and describes their multiple roles under physiological and pathological conditions, thus providing insights into treatment strategies. Additionally, it summarizes the advances and challenges in PARP‐targeted therapies and explores future directions for innovative therapeutic approaches. The findings may serve as a valuable resource for informing both clinical research and drug development.

Radon (Rn) exposure has a strong association with lung cancer risk and is influenced by epigenetic modifications. To investigate the characterization of DNA methylation (DNAm) episignatures for radon-induced lung cancer, we detected the specific changes in DNAm in blood and lung tissues using reduced representation bisulfite sequencing (RRBS). We identified the differentially methylated regions (DMRs) induced by radon exposure. The bioinformatics analysis of the DMR-mapped genes revealed that pathways in cancer were affected by radon exposure. Among them, the DNAm episignatures of MAPK10, PLCG1, PLCβ3 and PIK3R2 were repeated between lung tissue and blood, and validated by the MassArray. In addition, radon exposure promoted lung cancer development in the genetic engineering mouse model (GEMM), accompanied by decreased MAPK10 and increased PLCG1, PLCβ3, and PIK3R2 with mRNA and protein levels. Conclusively, radon exposure significantly changes the genomic DNAm patterns in lung tissue and blood. The DNAm episignatures of MAPK10, PLCG1, PLCβ3 and PIK3R2 have a significant influence on radon-induced lung cancer. This brings a new perspective to understanding the pathways involved in radon-induced lung cancer and offers potential targets for developing blood-based biomarkers and epigenetic therapeutics.