Search Results (604)

Background/Objectives: The Arabidopsis thaliana GDS1 (Growth, Development and Splicing 1) gene has recently been identified as a key regulator linking nitrate signaling to leaf senescence. However, a systematic analysis of the GDS1 gene family in maize (Zea mays L.) is lacking. This study aims to identify and characterize the ZmGDS1 gene family in maize, providing a foundation for functional studies on their roles in growth, development, and low-nitrogen-induced leaf senescence. Methods: Putative ZmGDS1 family members were identified by searching the maize B73 reference genome using BLASTP (version 2.11.0+) and HMMER (version 3.4), with the Arabidopsis GDS1 protein sequence as the query. Candidate sequences were verified for the presence of the conserved zf-CCCH domain using NCBI CD-Search and SMART. Phylogenetic relationships, gene structures, conserved motifs, chromosomal distribution, collinearity, and promoter cis elements were comprehensively analyzed using MEGA 11, TBtools (version 1.098), MEME (version 5.5.9), and PlantCARE. Phylogenetic trees were constructed using the maximum likelihood (ML) method with the LG+G+I model and 1000 bootstrap replicates. Results: Thirteen ZmGDS1 genes were identified, distributed unevenly across eight maize chromosomes. Phylogenetic analysis classified the ZmGDS1 proteins into four distinct groups (A–D), revealing a lineage-specific expansion in group D. While all members contained the conserved zf-CCCH domain, their motif compositions varied considerably; ZmGDS1.1 exhibited the most complex structure, whereas ZmGDS1.12 had the most simplified. Subcellular localization predictions indicated that most ZmGDS1 proteins are targeted to the nucleus, consistent with a potential role as transcription factors. Promoter analysis revealed an abundance of cis elements associated with light response, hormone signaling (methyl jasmonate, abscisic acid, auxin), and stress responses. Notably, phylogenetically related genes tended to share similar cis-element profiles. Conclusions: This genome-wide analysis provides the first characterization of the ZmGDS1 gene family in maize. The observed structural conservation and diversity, together with regulatory elements linked to senescence-associated signals, support the hypothesis that ZmGDS1 genes may contribute to leaf senescence, particularly under low-nitrogen conditions. These findings provide a basis for future functional validation studies. Full article

Background: Polyploid and chromosomal copy number gains (CNGs) cells may serve as key mediators of tumor plasticity, therapeutic resistance, and clonal evolution. Despite growing interest, their biological and clinical relevance in colorectal cancer, particularly in the metastatic setting, remains poorly defined. Methods: We performed an integrated morphological, cytogenetic, and genomic analysis of metastatic colon cancer. A tissue microarray comprising 100 tumors was evaluated, of which 47 cases were fully assessable for morphology and fluorescence in situ hybridization (FISH). Polyploid nuclei and chromosomal CNGs were assessed morphologically and cytogenetically. High-resolution targeted sequencing (TruSight Oncology 500) was conducted to characterize genomic alterations. Bioinformatic analyses included Gene Ontology enrichment and Phenolyzer network modeling. Associations with clinicopathological variables and survival outcomes were explored. Results: Polyploid nuclei and/or chromosomal CNGs were identified in approximately 25% of evaluable cases. These alterations were enriched in right-sided CRCs and in older patients, suggesting a link with age-related genomic instability. Polyploid/CNG tumors did not show significant enrichment for canonical CRC driver mutations (RAS, TP53, SMAD4), although trends toward co-occurrence with BRAF mutation and mutual exclusivity with HER2 amplification were observed. Integrative bioinformatic analyses highlighted dysregulation of pathways involved in mitotic control, centrosome organization, and DNA replication stress. Conclusions: In metastatic colon cancer, the presence of genome-wide copy number gain may delineate a tumor subset with distinctive clinicopathological and molecular characteristics. Further studies are warranted to elucidate the biological significance of these features and to explore their potential implications for tumor evolution, treatment response, and clinical stratification. Full article

The isolation of locally adapted rhizobial strains with high symbiotic activity represents an effective strategy for increasing soybean yield under extreme environmental conditions. In this study, seven novel strains were isolated from nodules of soybeans grown in a greenhouse using field soil from the Lower Volga region. Five genomes were assembled into complete circular chromosomes, whereas two strains yielded near-complete chromosomes containing single repeat-mediated junctions. All strains had putative plasmids that were independently validated as circular by long-read mapping and confirmed by the presence of characteristic replication and conjugation-associated genes. Genome sequences of strains were about 11 Mb, and GC contents were 63.1–63.3%. Comparative genome analyses demonstrated that all strains had average nucleotide identity values of 95.4% with Bradyrhizobium japonicum USDA 6^T and 96.3% with Bradyrhizobium barranii 144S4^T, forming a distinct cluster in phylogenetic trees. No significant differences were detected between B. japonicum and B. barranii that would explain the species boundary. Therefore, it is proposed to unite all novel strains into the subspecies Bradyrhizobium japonicum subsp. saratovii subsp. nov., and all other strains of B. japonicum and B. barranii we suggest dividing into four subspecies: Bradyrhizobium japonicum subsp. japonicum subsp. nov., Bradyrhizobium japonicum subsp. barranii comb. nov., Bradyrhizobium japonicum subsp. apii comb. nov., and Bradyrhizobium japonicum subsp. saratovii subsp. nov. The proposed taxonomic framework expands current knowledge of the biodiversity of soybean symbiotic bacteria and contributes to a better understanding of the distribution and the evolution of bacteria Bradyrhizobium spp. in previously unexplored regions. Full article

Background/Objectives: DNA polymerase ε (Pol ε), encoded by POLE1, plays a pivotal role in high-fidelity DNA replication and in coordinating DNA repair. While pathogenic exonuclease-domain variants are well established in cancer, biallelic POLE1 variants remain largely unexplored in non-malignant human cells. Methods: Here, we analyzed primary fibroblasts derived from a skin biopsy of a compound-heterozygous patient carrying two POLE1 variants. Western blot analysis confirmed detectable Pol ε protein levels, indicating preserved protein expression despite the underlying variants. Results: Nevertheless, functional alterations were observed across multiple independent assays. Compared with healthy control fibroblasts, this patient-derived Pol ε fibroblast line exhibited reduced clonogenic survival following ionizing radiation. Surviving fractions were consistently lower across radiation doses from 2 to 4 Gy, with an approximately twofold reduction at 2 Gy and progressively greater differences at higher doses. The isoeffect dose corresponding to 10% survival was reduced relative to pooled control fibroblasts. In addition, chromosomal breakage was increased, supporting altered processing of radiation-induced DNA damage in this cellular model. Live-cell imaging and senescence assays revealed delayed proliferation and an increased proportion of senescent or senescence-like cells under baseline and genotoxic stress conditions, including enhanced senescence-associated β-galactosidase activity. Flow-cytometric analysis demonstrated S phase accumulation and G2/M arrest, consistent with replication stress and cell-cycle perturbation. Immunofluorescence staining revealed increased γH2AX foci, consistent with persistent DNA double strand breaks. RAD51 foci formation was not reduced; instead, increased RAD51 recruitment was observed under combined cisplatin and irradiation treatment, arguing against a primary defect in RAD51-mediated homologous recombination. POLE1-variant fibroblasts also showed impaired proliferative recovery, reduced wound closure, increased γH2AX accumulation following cisplatin exposure, suggesting heightened susceptibility to DNA crosslinking stress. Conclusions: Collectively, these findings provide the first functional characterization of a patient-derived POLE1-variant fibroblast cell line and indicate that altered Pol ε function may influence cellular responses to genotoxic stress. While based on primary fibroblasts from a single compound-heterozygous patient, validation in additional patient-derived or isogenic models will be required to determine the broader relevance of these findings. Full article

Asparagine synthase (ASN) is a key enzyme in nitrogen metabolism. It is responsible for the synthesis of asparagine, but the function and molecular mechanism of its superfamily in the seed storage protein of soybean is not yet clear. In this study, a total of 34 members of the ASN superfamily were identified in soybean by in silico analysis (GmASNs). Phylogenetic and structural analyses show that most proteins in the GmASN superfamily contain conserved functional domains, which are predicted to be hydrophilic proteins, and are mainly located in the cytoplasm and chloroplasts, and a few are located in mitochondria. The chromosome distribution shows that they are randomly scattered on 13 chromosomes, and gene replication drives the expansion of the family. In addition, the haplotype analysis of four key GmASN superfamily genes (GmASN11, GmASN16, GmASN20, GmASN29) shows that they are significantly associated with the content of seed storage protein (SSP). Importantly, the aggregation of favorable haplotypes at these loci can significantly improve the SSP level. These results elucidate the evolutionary history of the GmASN gene superfamily and identify valuable haplotypes. These haplotypes are promising targets for the development of high-protein soybean varieties through marker-assisted breeding. Full article

Cell division is a highly regulated process that actively involves dynamic changes to the genetic material within the nucleus. DNA is faithfully replicated in the S-Phase of the cell cycle, being converted from loose, relaxed chromatin into tight, condensed chromosomes to be segregated in mitosis. In addition to scaffolding proteins that shape these mitotic chromosomes, post-translational modifications of histones within nucleosomes modulate chromosome dynamics throughout the cell cycle. In this review, we use a comparative approach to highlight some of the major epigenetic marks affected by the cell cycle during embryogenesis of Caenorhabditis elegans: H4K20me1, H3S10ph, H4S1ph, H2AS1ph, and H3T118ph. These five histone post-translational modifications will be specifically highlighted in the context of the mitotic cell cycle, as they are well documented in the C. elegans literature. Full article

Faithful DNA replication is essential for genome stability but is constantly challenged by metabolic and oxidative stresses. Hydroxyurea (HU), a widely used antiproliferative drug, is traditionally known to inhibit ribonucleotide reductase and deplete dNTP pools. Recent studies, especially in Saccharomyces cerevisiae, reveal that HU-induced replication stress also arises from reactive oxygen species (ROS), which oxidize DNA, impair iron–sulfur-dependent replication enzymes, and disrupt replisome function. These combined effects promote helicase–polymerase uncoupling, accumulation of RPA-coated ssDNA, and activation of the Mec1–Rad53 (ATR–CHK1) checkpoint, leading to strand-specific changes such as PCNA unloading and reduced lagging-strand synthesis. When protective pathways are overwhelmed, HU-treated forks collapse, generating chromosome breaks and genome instability. This review summarizes current understanding of how HU remodels replication forks through both ROS-dependent and ROS-independent pathways and highlights emerging insights into how these mechanisms influence genome stability and may be exploited for therapeutic benefit. Full article

G-quadruplexes (G4s) are specialized nucleic acid structures extensively formed throughout the genome, with particular enrichment in regulatory regions such as telomeres, promoters, and transcriptional enhancers. These four-stranded assemblies are involved in multiple chromosomal processes, including DNA replication, transcription, maintenance of genomic stability, and epigenetic regulation, and are closely associated with cancer biology. Due to their unusual thermodynamic stability, G4s serve as physical barriers to DNA/RNA unwinding, thereby impeding replication, transcription, and translation and compromising genome integrity. To mitigate this threat, cells have evolved dedicated helicases that can actively resolve G4 structures. In this review, we summarize recent structural advances—primarily derived from protein crystallography—regarding the mechanisms by which helicases unwind G4 quadruplexes. The insights presented herein establish a framework for elucidating the molecular basis of G4 unfolding and for the rational design of small-molecule G4 ligands and therapeutic agents. Additionally, we explore the applications of G4 helicases in nanopore sequencing, which aim to enhance sequencing accuracy, throughput, and continuity. Full article

Torsional stress from DNA supercoiling is receiving renewed attention as a driving force for chromosome folding and the establishment of gene activity states. Transcription is a major source of DNA supercoiling, while topoisomerases relax supercoils and solve topological problems that arise during DNA replication, transcription, and chromosome segregation. Recent technological advancements have allowed for the mapping of how torsional stress distributes within the genome and distinguishing between occupancy of topoisomerases on chromatin and sites where they are catalytically engaged. Coupling these innovations to assessments of 3D chromosome conformation and nascent transcription at high resolution have provided a new understanding of the relationships between supercoiling and topoisomerase activity. Here, we summarize the insights obtained from these recent studies and discuss how the interplay between transcription, supercoiling, and topoisomerases shapes cellular gene activity states. Full article

The Zinc Finger X-Linked Duplicate B (ZXDB) gene is one of a pair of replicated zinc finger genes on chromosome Xp11.21. The homologous gene of ZXDB in mice is Zxdb. Recent studies have found that Zxdb plays a role in the spermatogenic process of mice; however, its impact on the female reproductive system has not yet been explored. In our study, we found, for the first time, that the loss of function of Zxdb leads to reduced decidualization rates and a decrease in litter size in female mice. Secondly, we found that maternal loss of Zxdb is the determinant of these phenotypes. Thirdly, the transcriptional and proteomic differential expression genes in the uterine tissues of wild-type (WT) and Zxdb knockout (Zxdb-KO) mice were significantly enriched in signaling pathways such as adhesion molecules. Finally, we demonstrated that the disorder of expression and uneven distribution of adhesion molecules in mouse uterine tissue may be the main reason for the decline in embryo implantation rate. In conclusion, we have established for the first time a link between the Zxdb gene and reduced female fertility. This study will help provide guidance and genetic counseling for future common clinical complications such as Recurrent Spontaneous Abortion (RSA) or Recurrent Implantation Failure (RIF). Full article

Introduction: Telomeres, which protect chromosome ends, are important in cell replication and are altered by ageing. In the realm of organ transplantation, telomere length has emerged as a potential biomarker for predicting both graft survival and recipient longevity. This study explores the correlation of telomere length with transplant outcomes to assess whether longer telomere length is associated with better long-term graft function and patient survival. Methods: Telomere length (TL) was analysed in 274 European renal transplant pairs (donors/recipients). Recipient DNA was collected before and after kidney transplantation, and donor DNA just prior to transplant surgery. Results: Donor TL was not significantly associated with graft survival. Donor age was a significant predictor of graft failure (1.02, 95% CI: 1.01–1.03, p < 0.01). Post-transplant recipient TL had a significant association with graft survival. Longer TL was associated with an up to 90% reduction in risk of graft failure (HR = 0.10, 95% CI: 0.015–0.71, p = 0.02). Conclusions: In this study, kidney transplant recipients with longer telomere length demonstrated significantly better long-term graft survival. If validated in additional kidney transplant cohorts, recipient telomere length could serve as a valuable biomarker for improving graft failure risk stratification and enhancing the long-term care of transplant recipients. Full article

Cyclocybe chaxingu is a well-known edible fungus in China, in which pileus size and color are key traits determining its commercial value. However, the molecular genetic mechanisms underlying the morphological development of its pileus remains limited at present. To address this, our study first completed the high-quality genome assembly of the monokaryotic strain Ag.c0002-1 of albino C. chaxingu, anchoring it to 13 chromosomes via Hi-C technology. The final genome size was 51.7 Mb with a GC content of 51.06%, and 11,332 protein-coding genes were annotated. Phenotypic observations and comparative transcriptome analyses were then conducted on the pilei of the brown cultivar Ag.c0067 and the white cultivar Ag.c0002 at the primordium, elongation, and mature stages. Phenotypic analysis revealed continuous pileus expansion accompanied by progressive color lightening in both cultivars during development. Comparative transcriptomic analyses revealed significant differences in gene expression patterns between the two cultivars across developmental stages. KEGG enrichment analysis indicated that pileus expansion is closely associated with pathways related to DNA replication, cell cycle of yeast, carbon metabolism, and carbohydrate digestion and absorption. Among these, differentially expressed genes involved in cell division tended to be downregulated, whereas genes associated with energy metabolism and substance transport were upregulated, providing the necessary energy and material support for pileus growth. Changes in pileus pigmentation were primarily associated with tyrosine metabolism, betalain biosynthesis, tryptophan metabolism, and melanogenesis pathways. Notably, the downregulation of tyrosinase genes and the upregulation of glutathione S-transferase genes during development may represent major molecular mechanisms underlying pileus color lightening. Overall, this study provides important insights into the molecular mechanisms regulating pileus development and pigmentation in C. chaxingu, while also offering valuable theoretical support for genetic analysis of basidiomycete morphogenesis and the molecular breeding of edible mushrooms. Full article

Cytochrome P450 (CYP450) monooxygenases are a class of enzymes containing conserved heme-binding functional domain. They contribute to a wide range of biosynthetic processes, serving a pivotal function in plant resistance to abiotic stress. To date, little is known about the CYP450s of Chlamydomonas reinhardtii. In our study, a total of 37 crP450 genes were identified from C. reinhardtii based on domain and sequence alignment, unevenly distributed on 12 chromosomes with 4 pairs of tandem replications shared among family members. Most of these genes contained 10 or more introns and encoded CYP450 proteins with an average of 593 amino acids and 3–9 conserved motifs. CYP450 enzymes were mainly distributed in the chloroplasts, cytoplasms, mitochondria, and cytoplasmic membranes. There were numerous light, jasmonic acid, abscisic acid, and salicylic acid response elements located in the upstream of gene coding sequences, suggesting that these genes could be modulated by plant hormones. Transcriptome analysis uncovered distinct expression patterns of crP450 genes under various stress conditions, with the 37 crP450 genes grouped into 9 clusters. In summary, this study presented a genome-wide characterization of CYP450 genes in C. reinhardtii, providing a strong foundation for further exploration into their biological functions. Full article

Many cellular processes, including gene expression regulation, DNA replication and repair, as well as proper condensation and segregation of chromosomes, require highly coordinated remodeling of chromatin. Cohesin and condensins, the structural maintenance of chromosomes (SMC) protein complexes that function as ATP-powered loop extrusion motors, are key determinants of chromatin structure. The genetic loss of their function is lethal, whereas inducible degradation approaches enable rapid, robust analysis of the depletion phenotype. In this review, we discuss new insights into chromatin folding through each cell cycle phase from the auxin-inducible degradation (AID) system. We review the mechanisms by which condensins and cohesins contribute to the helical organization of mitotic chromosomes and to the maintenance of chromosome territories in interphase. Additionally, we discuss studies examining the roles of TOP2A, KIF4A, and SRBD during mitosis using the AID system. We then outline emerging principles of the mitotic-to-interphase transition and how targeted degradation of chromatin proteins reshapes this process. Finally, we highlight and discuss new advances in understanding interphase chromatin organization revealed by AID-based studies. Full article

Xeroderma Pigmentosum group C (XP-C) is an autosomal recessive disorder caused by mutations in the XPC gene, leading to defective nucleotide excision repair. This defect leads to genomic instability and a profound cancer predisposition. To model this disease, we generated induced pluripotent stem cells (iPSCs) from an XP-C patient carrying a novel homozygous nonsense mutation in the XPC gene (c.1830C>A). The resulting iPSCs demonstrated typical pluripotent characteristics, including expression of key markers and trilineage differentiation capability. However, genomic assessment revealed progressive karyotypic instability during extended culture. While initial whole-genome sequencing detected no major chromosomal abnormalities, subsequent G-banding analysis identified acquired trisomy 12 in two lines (CL12 and CL27) and a derivative X chromosome in a third line (CL30). These abnormalities were absent in early-passage analyses, indicating that they were acquired and selected for during extended culture. The acquisition of a derivative X chromosome in CL30, alongside recurrent trisomy 12, represents a unique cytogenetic signature likely attributable to the underlying XPC defect. We hypothesize that the loss of GG-NER creates a permissive genomic environment, accelerating the accumulation of DNA damage and chromosomal missegregation under replicative stress. This temporal divergence in genomic integrity highlights how culture pressures drive chromosomal evolution in XP-C iPSCs independently of initial reprogramming. Our findings emphasize that XP-C iPSCs require continuous genomic surveillance and provide a model for investigating how DNA repair deficiencies interact with in vitro culture stress. Full article