Search Results (61)

Cutaneous melanoma and basal cell carcinoma (BCC) represent the two primary malignancies driven by solar ultraviolet (UV) radiation. To map the spatial topology and distance dependence of their mutational signatures, we deployed new analytical bioinformatics workflow utilizing two convergent strategies: a data-driven read-level phasing framework to discriminate between collateral mutational events versus independent ones and a hypothesis-driven spatial permutational simulation model to capture density-dependent local deviations. A whole-genome analysis employing this framework unexpectedly reveals two fundamentally distinct lesion-processing landscapes, present in both BCC and melanoma. While independent mutations consistently reproduce canonical UV signatures (SBS7a–c) in both tumor types, collateral mutations tell a distinct and more varied narrative between BCC and melanoma. These collateral mutations are unusually abundant for non-UV characteristics, such as age-related SBS1 and SBS5, and display a notable 3′ to 5′ asymmetry near UV-induced lesions in pyrimidine dimers. We also demonstrated that BCC displays a pronounced enrichment of dinucleotide base substitutions flanking UV-signature sites on the 3′ side, particularly CA>TG and CG>TA changes. Ultimately, these topological patterns in both tumors indicate that a primary photoproduct seeds secondary mutagenesis within its local chromatin environment, dramatically altering our understanding of UV-induced lesion processing. Full article

Banana Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), poses a severe threat to global banana production, and breeding resistant cultivars remains the most effective control strategy. Mutation breeding, including radiation mutagenesis and somaclonal variation, has become a primary approach for developing resistant germplasm in triploid Cavendish bananas. However, whether secondary bud-sport selection from resistant somaclonal lines inadvertently compromises original resistance mechanisms at the molecular level remains poorly understood. In this study, we generated 44 mutants from Baxi jiao via ⁶⁰Co γ-irradiation and selected five lines with distinct phenotypic variations. We also collected somaclonal variant lines GCTCV-218, GCTCV-119, GCTCV-105, their bud-sport derivatives (NK_No.1, NTH, RK_No.1), and the radiation-induced resistant mutant ‘Zhongre No.1’. Using whole-genome resequencing and transcriptome analysis, we systematically compared the genetic and transcriptomic outcomes of these breeding strategies. Radiation mutagenesis induced substantial genomic structural variations and generated novel expression patterns of defense-related genes. In contrast, while bud-sport derivatives of GCTCV-218 remained genetically similar to their parent, they exhibited significant downregulation or loss of key resistance gene expression, particularly PR-1 family members. Our findings reveal that phenotype-driven somaclonal selection can inadvertently erode original resistance mechanisms, and we recommend prioritizing radiation mutagenesis for developing banana cultivars with stable and durable resistance to Foc TR4. Full article

Background/Objectives: Pancreatic ductal adenocarcinomas (PDACs) are lethal tumors exhibiting resistance to most cancer therapeutics, particularly DNA-damaging agents. The KRAS oncogene drives PDACs, and many of these tumors are addicted to it and its downstream effectors. One such effector is Rac1, a small GTPase involved in actin cytoskeleton remodeling and regulation of the DNA damage response. We previously showed that Rac1 inhibition blocks activation of ATM/Chk2 and ATR/Chk1 pathways in response to gamma rays, sensitizing PDAC cells to radiation. Methods: Western blot analyses were used to assess the impacts of Rac1 inhibition on the components of the ATR/Chk1 cascade. Results: Here, we show that Rac1 inhibition disrupts ATR/Chk1 signaling by promoting degradation of Claspin, a key component of the fork protection complex needed for the Ser345-phosphorylation of Chk1 by ATR. In PDACs and normal pancreatic ductal cells, Rac1 inhibition (via inhibitors or siRNA) decreased Claspin protein levels without affecting its mRNA, reflecting a >3-fold reduction in Claspin’s half-life. Claspin contains a phosphodegron recognized by SCF^βTrCP E3 ubiquitin ligase when phosphorylated at Ser30/Ser34, a process involving PLK1 kinase. In PDAC cells, Claspin degradation upon Rac1 inhibition required the proteasome and βTrCP1/2 proteins, and was blocked by the mutagenesis of Ser30/Ser34, but occurred independently of PLK1 activity. Although Rac1 inhibitors reduced Claspin in both normal and cancer cells, PDAC cells may be uniquely vulnerable due to elevated replication stress and greater reliance on ATR/Chk1. Accordingly, Claspin depletion sensitized PDAC cells but not normal cells to gamma rays, inducing apoptosis only in cancer cells. Conclusions: These findings identify Rac1 as a critical regulator of ATR/Chk1 signaling through stabilization of the fork protection protein Claspin. Rac1 inhibition promotes the βTrCP-dependent, proteasome-mediated degradation of Claspin via its phosphodegron, thereby impairing Chk1 activation in response to DNA damage. Full article

Background: Ultraviolet-C (UV-C) radiation is a high-energy physical mutagen capable of inducing DNA damage and oxidative stress, thereby generating genomic variability in photosynthetic organisms. However, its genome-wide effects in unicellular eukaryotic microalgae remain poorly characterized. This study developed a UV-C mutagenesis protocol in Chlamydomonas reinhardtii and evaluated its genomic and physiological impacts. Methods: Axenic cultures of Chlamydomonas reinhardtii (137c+) were exposed to UV-C (100–280 nm) for 12, 48, and 96 min. Viable colonies were analyzed by Random Amplification of Polymorphic DNA PCR (RAPD-PCR) to assess genetic variability, while chlorophyll content and the expression of stress-responsive genes were measured via spectrophotometry and Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR), respectively. Results: UV-C treatment induced extensive genomic polymorphism with heterogeneous clustering patterns independent of exposure time, consistent with stochastic mutagenesis. Several mutants exhibited reduced chlorophyll content, indicating impaired photosynthetic efficiency. In contrast, one genotype (pop18) maintained wild-type chlorophyll levels despite marked genetic divergence, coupled with upregulation of antioxidant, DNA repair, and stress-response genes. Conclusions: Overall, UV-C irradiation represents an effective approach to generate non-directional genomic variability in Chlamydomonas reinhardtii, with evidence that random mutagenesis can drive functional reorganization of stress-response pathways, supporting its application in microalgal strain improvement. Full article

Background/Objectives: Exposure of cells to ionizing radiation induces isolated DNA lesions, including single-strand breaks, apurinic/apyrimidinic sites, and oxidized bases, as well as clustered damages of different complexity. The latter types of damage are difficult to repair, and the failure to process them accurately and efficiently is related to the induction of mutagenesis, genomic instability, cancer, and aging. Since various types of clustered lesions may occur simultaneously after radiation exposure, leading to a complex architecture of DNA damage, the study of the concomitant formation and the removal kinetics of clustered DNA damage is important to determine the mutagenic and, consequently, the carcinogenic potential of ionizing radiation. Methods: With the aim of capturing real-time coexisting lesion types and assessing the repair kinetics of clustered damages, the simultaneous determination of double-strand breaks, apurinic/apyrimidinic site clusters, and oxypurine clusters induced by γ-irradiation of Saccharomyces cerevisiae yeast cells was performed immediately after exposure and at time intervals during incubation in Liquid Holding Recovery conditions. Results: Ionizing radiation induced lethal and mutagenic events, leading to a dose-dependent linear increase in double-strand breaks, apurinic/apyrimidinic site clusters, and oxypurine clusters. The kinetic study showed that double-strand break frequencies declined during Liquid Holding Recovery, although a transient increase was detected at early time points. At 160 Gy, apurinic/apyrimidinic site clusters repair was evident, whereas at 400 Gy the frequency of damage increased before returning to the initial value at 24 h. In contrast, oxypurine clusters showed no net increase in repaired lesions over 24 h. Conclusions: The complex nature and topological characteristics of ionizing radiation-induced clustered DNA damage may influence lesion processing. Also, ionizing radiation may disrupt redox cellular homeostasis, leading to DNA damage and delayed effects. Full article

The use of microalgae as a food source is limited by consumers’ dislike of their organoleptic traits, primarily the intense green color and bitter taste associated with high chlorophyll content. The eukaryotic microalgae Chlorella vulgaris can grow under heterotrophic conditions, providing the opportunity to cultivate chlorophyll-less strains. In this work we applied random mutagenesis for breeding chlorophyll-deficient C. vulgaris strains. Wild-type strain was UVC-radiated, and 12 colonies with changed pigmentation were selected. Based on phenotypic stability two mutants, M6 and M11, were selected for characterization of growth, pigment and biomass accumulation. Cultivation under photo-, mixo- and heterotrophic conditions revealed distinct phenotypes for the two mutants. M6 remained chlorophyll-deficient in all cultivation conditions tested, while chlorophyll was observed in M11 when grown under light. Under heterotrophic and mixotrophic growth conditions, both mutants were chlorophyll-deficient while biomass productivity, protein content, and amino acid composition remained similar to wild type. Characterization of the cellular ultrastructure of the wild type and mutants using cryo Focused Ion-Beam Scanning Electron Microscopy revealed that functional chloroplasts and thylakoid membranes were absent in the mutants. Our work demonstrates how a simple approach using UV mutagenesis and visual screening can provide novel strains of C. vulgaris with traits for improved consumer acceptance, without compromising the use of the algae biomass as a protein-rich food source. Full article

Astaxanthin, one of the most commercially valuable carotenoids, is renowned for its potent antioxidant and anti-inflammatory properties and is experiencing growing demand across diverse industries. To enhance astaxanthin production in Paracoccus marcusii, compound mutagenesis was performed using ethyl methanesulfonate (EMS), ultraviolet (UV) radiation, and atmospheric room temperature plasma (ARTP) treatment. Subsequently, a high-throughput microbial microdroplet culture (MMC) system was employed to select fast-growing microdroplet, followed by screening for high astaxanthin-producing mutants on dual-inhibitor plates. The mutant M21 was isolated and exhibited a significant increase of 16.86% in astaxanthin content (1.53 mg/g) and a 19.81% increase in astaxanthin production (11.71 mg/L) compared with the wild type (WT) (p < 0.05). Moreover, the enhanced phenotype of M21 was genetically stable. Response surface methodology (RSM)-based optimization of fermentation conditions further increased astaxanthin content and production to 1.72 mg/g and 12.92 mg/L, respectively, corresponding to improvements of 16.44% and 23.02% over the WT, while simultaneously reducing culture time, total nitrogen requirements, and sodium lactate consumption, thereby lowering production costs. This study achieved significant enhancement of astaxanthin production through novel mutant breeding and fermentation optimization, underscoring the effectiveness of this integrated strategy for application in industrial biotechnology. Full article

(1) Background: Cutaneous secondary malignant neoplasms are a growing survivorship burden after pediatric cancers and hematopoietic stem cell transplantation (HSCT), yet skin-focused surveillance remains inconsistently implemented. (2) Objective: To synthesize current molecular dermatology insights relevant to prevention, early detection, and treatment of basal cell carcinoma (BCC) in high-risk survivors, while anchoring the discussion in a detailed case of multiple BCCs after childhood acute lymphoblastic leukemia and HSCT. (3) Methods: Narrative review integrating clinical, dermoscopic, molecular, and translational data from recent high-impact studies; case retained in full. (4) Results: Radiation exposure (especially total body irradiation), prior immunosuppression, and persistent immune dysregulation synergize with ultraviolet mutagenesis to create a “field cancerization” state characterized by Hedgehog-pathway activation (Patched1/Smoothened), impaired Deoxyribonucleic Acid damage response, and stromal remodeling. Dermoscopy, when embedded in routine whole-body examinations, markedly improves accuracy for keratinocyte cancers. Chemoprevention (e.g., nicotinamide) and targeted therapies (hedgehog inhibitors; Programmed Death-1 blockade) represent key translational levers for care innovation. (5) Conclusions: Integrating structured dermatologic surveillance with molecularly informed prevention and therapy should be standard in survivorship pathways for hematopoietic stem cell transplantation/Radiotherapy-exposed patients. Full article

Background: Chili pepper (Capsicum annuum L.), a globally cultivated and ancient domesticated crop, carries considerable significance in agriculture. While radiation-induced mutagenesis has found application in this crop, the mutagenic efficacy and molecular-level impacts of 7Li ion beam radiation remain poorly elucidated. Methods: We irradiated pepper with a beam of 7Li ions to create a mutant, which showed good economic traits, and phenotypic and physio-biochemical characterization were combined with proteomic and metabolomic profiling to delineate the mutagenic mechanisms. Quantitative real-time PCR (qRT-PCR) was further utilized to assess the biological impact and underlying response pathways. We used this to evaluate the biological impact and the reaction mechanisms behind it. Results: 7Li beam radiation positively influenced morphology and physiological traits, notably chlorophyll and anthocyanin content. Leveraging proteomic profiling detected 6082 proteins, including 355 differential proteins (139 upregulated, 216 downregulated), enriched in 4 KEGG pathways. Based on GO and KEGG network analysis, 250 metabolites were quantified, with 120 being differentially abundant (112 upregulated, 8 downregulated), enriched in 9 metabolic pathways. Furthermore, qRT-PCR results revealed that differentially expressed genes were consistent with the corresponding metabolomic data. Joint analysis revealed the coordinated enrichment of differential metabolites and proteins in pathways related to amino acid and carbohydrate metabolism. These findings suggest that these active pathways in pepper are related to its response to ion beam radiation. Overall, this study is a valuable resource for subsequent genomic research on peppers and 7Li ion beam radiation research. Full article

The nopal cactus, a plant from the Cactaceae family, holds significant economic and nutritional value for Mexico. This study aimed to enhance the genetic diversity and morphological traits of Opuntia velutina, a species cultivated as a vegetable nopal. A total of 1050 in vitro O. velutina explants were exposed to 15 different doses of gamma radiation from ⁶⁰Co gamma, ranging from 5 to 125 Gy. The lethal dose was above 50 Gy, with an LD₅₀ of 22.8 Gy for stimulating in vitro shoot growth. Shoots derived from doses between 5 and 50 Gy were subjected to in vitro shoot proliferation across four consecutive generations to stabilize morphological traits. Cluster analysis categorized the 178 irradiated shoots into 13 distinct morphological groups (CG1–CG13). Twenty-seven shoots exhibiting significant morphological improvements, such as a 50–100% increase in cladode length, up to a six-fold increase in shoot number, and up to a seven-fold increase in root number, were selected for molecular analysis of genetic diversity. Six primers were used with the Inter Simple Sequence Repeat (ISSR) molecular markers to examine genetic uniformity, yielding 54.5% polymorphic bands, indicating a high level of genetic variation. Both a UPGMA dendrogram and STRUCTURE-based Bayesian analysis confirmed the genetic divergence among the selected mutant lines. Overall, gamma irradiation effectively enhanced both phenotypic and genotypic diversity in O. velutina. This study corroborates that in vitro mutagenesis through gamma radiation is a viable strategy for generating novel genotypes with breeding potential within the Opuntia genus. Full article

Ultraviolet (UV)-induced mutagenesis is a cost-effective and straightforward technique for introducing random genetic variations without the use of chemical reagents or genetic engineering. It is commonly employed to enhance enzyme activity in industrial trains. In this study, Trichoderma sp. was exposed to UV radiation at varying distances (4, 9, and 13 cm) and durations (2, 4, 6, and 8 min) to induce mutations. The activities of endoglucanase (EG), β-glucosidase (BGL), and cellobiohydrolase (CBH) were assessed following treatment. The 4 cm exposure distance yielded the highest enhancement, with EG, BGL, and CBH activities increasing 1.5-, 1.3-, and 0.9-fold, respectively. When the distance was fixed at 4 cm, the optimal exposure time was identified as 4 min, yielding further enhancements of 1.9-, 1.6-, and 1.4-fold, respectively. The resulting mutant, designated Mut-4, was scaled up in a 10-L bioreactor to assess its industrial applicability. Mut-4 retained its enhanced performance, achieving 1.9-, 2.0-, and 1.4-fold enhancements in EG, BGL, and CBH activities, respectively, compared with the original strain. These findings indicate that combining UV-induced mutagenesis with basic screening is an effective strategy for enhancing cellulolytic enzyme production, representing a promising approach for lignocellulosic biomass conversion. Full article

The increasing incidence of cutaneous squamous cell carcinoma (cSCC), together with the ominous risks of metastasis and recurrence, underscores the importance of identifying novel therapies and validated biomarkers to augment patient management, particularly in the context of well-established and advanced disease. Following a brief overview of the well-recognized epidemiology, clinical features, and diagnosis of cSCC, the current review is focused on risk factors, most prominently excessive exposure to ultraviolet radiation (UVR) as a cause of persistent, pro-tumorigenic mutagenesis, and immune suppression. The next phase of the review encompasses an evaluation of the search for key driver mutations in the pathogenesis of cSCC, including the role of these and other mutations in the formation of immunologically reactive neoepitopes. With respect to additional mechanisms of tumorigenesis, immune evasion is prioritized, specifically the involvement of cell-free and infiltrating cellular mediators of immune suppression. Prominent amongst the former are the cytokine, transforming growth factor-β1 (TGF-β1), the prostanoid, prostaglandin E2, and the emerging immune suppressive nucleoside adenosine. In the case of the latter, tumor-infiltrating and circulating regulatory T cells have been implicated as being key players. The final sections of the review are focused on an update of the immunotherapy of established and advanced disease, as well as on the search for novel, reliable lesional and systemic biomarkers with the potential to guide patient management. Full article

Excessive exposure to ultraviolet B (UVB) radiation can lead to skin damage, such as erythema and swelling. Echinacoside is a key effective ingredient of medicinal plant Cistanche deserticola commonly used for therapies and treatments for anti-aging and irradiation-related skin diseases. However, the molecular mechanism underlying the action of echinacoside remains unclear. Here, we report that echinacoside ameliorates UVB-induced skin damage by directly acting on the Ca²⁺-permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) channel. Topical application of echinacoside efficaciously suppresses skin lesions induced by UVB radiation in wild-type mice but has no additional benefit in Trpv3 knockout mice. In whole-cell patch clamp recordings, echinacoside selectively inhibits TRPV3 channel currents induced by 2-aminoethoxydiphenyl borate in a concentration-dependent manner with an IC₅₀ value of 21.94 ± 1.28 μM. The single-channel patch clamp results show that echinacoside significantly reduces the open probability and open frequency without significantly altering TRPV3 channel unitary conductance. Molecular docking and site-specific mutagenesis indicate that residue T636 on the p-loop and residue T665 on the S6 segment of TRPV3 are critical for echinacoside binding to TRPV3. Taken together, our findings provide a molecular basis for further studies as use of natural echinacoside in irradiation-related skin care therapy, thus establishing a significant role of the TRPV3 channel in acute skin injury. Full article

Wheat, a staple crop cultivated for over 8000 years, sustains more than 2.5 billion people globally, as a major source of carbohydrate, protein, fiber, and essential nutrients. Colored wheat, enriched with dietary fiber and antioxidants, offers valuable genetic resources for developing functional wheat varieties. Herein, a mutant pool of 1069 colored wheat lines was developed through gamma-ray irradiation to enhance genetic diversity. Mutant lines were classified into 10 groups based on seed color parameters (L*, a*, and b*), which were measured using the Hunter Lab system. K-means clustering categorized the mutant lines, and four representative lines from each group were analyzed for agronomic traits (plant height, spike length, thousand-seed weight, and kernels per spike) and antioxidant properties (radical-scavenging activity, ferric reducing antioxidant power, and total antioxidant capacity). Principal-component analysis revealed distinct clustering patterns, indicating associations between seed color, agronomic traits, and antioxidant activity. Darker seed color groups exhibited 3–16% higher levels of bioactive compounds and 10–18% higher antioxidant activities, whereas lighter groups showed 8–42% lower functional potential compared to the control wheat. These findings highlight the potential of mutation breeding in generating phenotypic diversity and developing wheat varieties with improved functional traits and bioactive compound content. Full article

Mutagenesis breeding, combined with the application of corresponding herbicides to develop herbicide-resistant rice germplasm, provides great promise for the management of weeds and weedy rice. In this study, a topramezone-resistant rice mutant, TZR1, was developed from the indica rice line Chuangyu 9H (CY9H) through radiation mutagenesis and topramezone selection. Dose–response curves revealed that the resistance index of TZR1 to topramezone was 1.94-fold compared to that of CY9H. The resistance mechanism of TZR1 was not due to target-site resistance. This resistance could be reversed by a specific inhibitor of glutathione S-transferase (GST). The activity of antioxidant enzymes was analyzed. SNPs and Indels were detected using whole-genome resequencing; differentially expressed genes were identified through RNA sequencing. Then, they underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Key candidate genes associated with topramezone resistance were validated via a real-time quantitative PCR assay. Five GST genes, two UDP-glycosyltransferase genes, and three ATP-binding cassette transporter genes were identified as potential contributors to topramezone detoxification in TZR1. Overall, these findings suggest that GST enzymes possibly play an important role in TZR1 resistance to topramezone. This study will provide valuable information for the scientific application of 4-hydroxyphenylpyruvate dioxygenase inhibitors in paddy fields in future. Full article