The XPG endonuclease is crucial for nucleotide excision repair (NER) and other genome maintenance pathways. Precise regulation of XPG recruitment and activity during DNA repair is essential to avoid erroneous DNA incisions and genomic instability. In this study, we employed live-cell imaging to investigate how XPG is regulated during NER, focusing on its dynamic interactions with key factors involved in the pre- and post-incision steps. We found that TFIIH and XPA facilitate recruitment and association of XPG with DNA damage and that XPG localizes separately from TFIIH to UV-induced lesions. Furthermore, our results show that XPG's dissociation from DNA damage is triggered by its own incision activity as well as by that of XPF. Additionally, the exonuclease EXO1 promotes XPG dissociation, likely by processing incised DNA, even in the absence of XPG-mediated incision. Our findings help to better understand the regulatory mechanisms that control XPG activity during NER and provide important insights into the complex dynamics of the repair process.

The association between telomere length and expression of DNA repair genes as a biological trace of cumulative lifetime stress.

Enhanced environmental stress tolerance in reoccurring, emerging, and persistent (REP) Escherichia coli O157:H7 strains from leafy green associated outbreaks.

Deciphering transcriptomic insights into climate adaptation in Etroplus suratensis (pearl spot) under combined thermal-saline stress.

Damage response and postnatal compensatory repair in the male offspring mouse reproductive system following gestational cadmium exposure.

Emerging evidence has implicated non-SMC condensin I complex subunit H (NCAPH) as a key regulator of mitosis and driver of tumorigenesis. However, its expression profiling and clinical relevance in endometrial cancer (EC) remain inadequately characterized. The present study aimed to systematically investigate the expression profiling, mutational landscape, co-expression networks and prognostic importance of NCAPH in EC through integrated bioinformatics approaches. NCAPH expression was evaluated in pan-cancer and EC cohorts derived from The Cancer Genome Atlas and Genotype Tissue Expression databases. Mutational analysis was performed using the 'maftools' package in R software. Genes co-expressed with NCAPH (with a significance threshold of P<0.05) were subjected to functional enrichment analysis using Metascape. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to evaluate the correlation between gene expression and pathway scores. The Tumor Immune Estimation Resource database was utilized to explore the correlation between NCAPH expression and the abundance of tumor-infiltrating immune cells in EC. The prognostic importance of NCAPH was assessed by Kaplan-Meier survival analysis and receiver operating characteristic curve analysis. Immunohistochemistry and western blotting was performed to validate NCAPH protein expression in clinical specimens. Results indicated that NCAPH mRNA and protein expression were significantly elevated in EC compared with normal endometrium. In addition, NCAPH expression was found to be positively correlated with advanced International Federation of Gynecology and Obstetrics stage, advanced age, TP53 mutation and aggressive histological subtypes. Somatic mutations of NCAPH occurred in 4.92% of EC cases, with missense mutations being the predominant type (79.3%). Functional enrichment analysis indicated that NCAPH-associated genes were involved in 'cell cycle', 'DNA replication' and 'oocyte meiosis'. ssGSEA exhibited a positive correlation between NCAPH and DNA repair, G2M checkpoint, tumor cell proliferation and the PI3K/AKT/mTOR pathway. NCAPH expression exhibited a significant negative correlation with CD8+ T cell infiltration, whereas positive correlations were observed with CD4+ T helper 2 cell infiltration, CD163 and programmed death-ligand 1. In addition, high NCAPH expression was found to predict reduced 5-year overall survival and exhibited certain diagnostic efficacy (area under the curve=0.628). Overall, NCAPH may promote endometrial carcinogenesis through dysregulation of mitotic processes, induction of chromosomal instability as well as modulation of the tumor immune microenvironment and thus may serve as both a prognostic biomarker and a therapeutic target in EC.

FGFR1 drives metabolic adaptation associated with temozolomide resistance in glioblastoma.

LOXL4 drives radiotherapy resistance and immunosuppression in glioma by targeting SOCS3 for degradation to activate STAT3 signaling.

Skin is among the most frequent sites of cancer diagnosis, and the global incidence of skin cancer continues to rise despite extensive public health initiatives and preventive strategies. Arsenic, a ubiquitous environmental metalloid classified as a Group 1 carcinogen, remains an important concern due to widespread exposure through contaminated drinking water, food sources and occupational contact. Arsenic‑associated skin carcinogenesis involves complex, interdependent molecular processes and has been linked to the disruption of redox signalling, altered DNA damage signalling and repair responses as well as epigenetic reprogramming. In keratinocytes, arsenic perturbs redox and stress‑response pathways and may disrupt genome maintenance and cellular stress signalling in experimental systems. Arsenic may also alter microRNA networks and affect telomere and mitochondrial homeostasis, although the contribution of these processes to malignant transformation remains context‑dependent; in melanoma, the carcinogenic mechanisms of arsenic are less well characterized. Clinically, arsenic is recognized as a carcinogen in non‑melanoma skin cancer (NMSC) and evidence from high‑exposure endemic regions, together with occupational cohorts, suggest a dose‑responsive association. For melanoma, clinical evidence is more heterogeneous and subject to substantial potential confounding, although some studies suggest modest risk elevation in high‑exposure or occupational settings. Collectively, convergent mechanistic, experimental and epidemiological data support arsenic as an independent carcinogen, particularly in NMSC. These findings underscore the need for heightened clinical vigilance, particularly in exposed populations, and call for renewed public health strategies and regulatory frameworks to mitigate the persistent global burden of arsenic‑associated skin cancer.

Thyroid cancer and double-strand DNA break repair: The potential role of the MRN complex pathogenic variants.

Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer.

DLGAP5 protects glioblastoma cells against DNA damage through E2F1-transcripted RAD51AP1.

Novel HBx-interacting host cellular factors regulate dynamic nuclear and cytoplasmic localization of Hepatitis B virus X protein (HBx).

PARP14 as a master regulator of immune signaling and tumor microenvironment remodeling.

The current study investigated the antimicrobial mechanisms of Pulsed Electric Fields (PEF) by evaluating the resistance of 22 Escherichia coli K12 mutants. Initial screening at PEF treatment (23kV/cm, 53.3 μs, 95.4kJ/kg), pH 7.0, revealed increased sensitivity (p<0.05) of ΔclpB, ΔrpoS, and ΔdnaK expressed in Log10 reductions. Further inactivation kinetic analysis of 8 selected strains at pH 7.0 and 4.0 revealed a non-linear, polyphasic behaviour. This was described by a global modelling approach combining a log-linear primary model with a second-order polynomial model incorporating treatment time, total specific energy, and survival data as variables. The calculated model parameters (C1, C2, and C3) significantly differed (p<0.05) among strains at pH 7.0, but not at pH 4.0. Furthermore, the calculated inactivation rates, kmax, varied in relation to the total specific energy. At pH 7.0, kmax was higher at low (0-40kJ/kg) and high (140-180kJ/kg) total specific energies, while at pH 4.0, it raised at high total specific energies (120-160kJ/kg). In conclusion, E. coli response to PEF was dependant on the stress regulator rpoS. This response also involved genes which encode molecular chaperones such as dnaK, clpB and recA, related proteins for DNA repair. In conclusion, resistance to PEF was found to be influenced by pH and total specific energy, indicating that E. coli mounts a multifaceted response to PEF treatments, informing advanced microbial inactivation strategies for food safety.

The mismatch repair (MMR) system is an essential DNA repair mechanism that recognizes and corrects single base-base mismatches and unpaired nucleotides that escaped the proofreading exonuclease activity of DNA polymerases or recombination intermediates. This pathway is highly conserved throughout evolution. However, the nature and number of MMR proteins differ between eukaryotes and prokaryotes. Even more, the plant MMR system contains an ancient duplicated MMR protein. In addition, developmental processes vary among eukaryotic organisms. One striking feature is plant genome stability maintenance over multiple generations because embryogenesis and seed development occur after many divisions during plant vegetative growth. Thus, it was of our interest to review the present state of knowledge with respect to the MMR mechanism from eukaryotic organisms, with special comparisons between human, yeast, and plant systems.

Aggressive and therapy-resistant cancers present a significant challenge to treatment and are associated with poor patients' survival. Identifying molecular pathways and compounds that target these pathways is critical for improving patient outcomes. RNF4, an E3 Ubiquitin ligase, is pivotal for tumorigenesis in part by stabilizing oncoproteins and its role in DNA repair, thereby enhancing cancer cell survival and driving tumorigenesis. Elevated RNF4 levels are associated with poor prognosis in patients with carcinomas, melanoma, and sarcoma. Here, we describe the design and development of R4VPs, dual degrader compounds connecting two E3 ubiquitin ligases; Von Hippel-Lindau protein (VHL) with RNF4. R4VPs promote RNF4 degradation and thereby reduce the levels of its stabilized phosphorylated oncoproteins, while concomitantly eliminating VHL. R4VPs selectively induce ferroptotic cell death in cancer cells, sparing non-tumorigenic and primary cells in part by binding and modifying the anti-ferroptotic selanoproteins GPX4. R4VPs-induced ferroptosis preferentially targeting cells harboring tumor-driving mutations in the EGFR pathway, whereas it does not affect PI3K-transformed cells. As a consequence, R4VPs effectively induce cell death in Receptor Tyrosine Kinase inhibitor-resistant melanoma and primary patient sarcoma cells. Our findings highlight the potential of selective ferroptosis inducers, such as R4VPs, as a therapeutic strategy for hard-to-treat cancers.

Genetic architecture of multiple myeloma: From somatic alterations to germline susceptibility and clinical implications.

Analysis of B cell dynamic changes and pivotal drivers based on single-cell transcriptome of peripheral blood in sepsis.

Harnessing the HMnO2 nanoparticles as the DNA injury amplifier to improve the OXA-based trans-artery infusion chemotherapy.