DNA2 (DNA Replication Helicase/Nuclease 2)

This work presents an innovative sensing platform that combines near-infrared light-excited luminescence with nanozyme-mediated signal amplification for the detection of proGRP. The method surpasses conventional assays in sensitivity and operational stability, showing great promise for clinical translation. Its robust performance in serum underscores potential applications in early cancer diagnostics and biomarker-based disease management, providing a valuable tool for disease diagnosis.

IFI16 acts directly at stalled replication forks to protect nascent DNA from degradation by the nucleases MRE11, EXO1, and DNA2. Furthermore, IFI16 is required for the interferon-mediated rescue of fork protection in BRCA-deficient cells, highlighting the critical role of IFI16 in the crosstalk between innate immunity and fork protection during replication stress.

Furthermore, the sensor exhibited excellent reproducibility, stability, and specificity, achieving recoveries of 93.3-107.0% in spiked serum samples. The developed platform offers strong potential for the detection of HBV DNA and can be extended to other pathogenic nucleic acids and clinically relevant biomarkers.

Knockdown of GNL3 sensitizes HR-proficient breast cancer cells to etoposide or Olaparib treatment. Together, our results reveal that GNL3 SUMOylation is crucial for HR repair and suggest that targeting GNL3 SUMOylation may induce HR deficiency, thereby sensitizing breast cancers to DNA damage-inducing agents.

Importantly, the machine learning is adopted to explore the potential pattern hidden in PEC data, and the accuracy, sensitivity and specificity of circRNA intelligent diagnosis all reach 100 %. Machine learning-assisted renewable polarity-switchable PEC biosensor provides a new approach for circRNA analysis and early intelligent diagnosis of cancer.

Impact statement BRCA2, MRE11-RAD50, and WRN-DNA2 encode human proteins that process replication forks and result in distinct genetic instabilities and cancers when mutated. Here, we show their bacterial homologs act on unique replication fork substrates-those at DNA damage sites or as replication completes, and discuss their possible functional conservation in humans.

Dna2 mutants demonstrated significant sensitivity to replication stress induced by MMS, hydroxyurea, topotecan, and nitrogen mustard. Dna2lS/S1 mutants exhibited higher survival than Dna2lS/D2 upon exposure to topotecan and bleomycin, suggesting a possible helicase-specific role in damage response...These insights clarify the nuanced contributions of the nuclease and helicase domains of DNA2, suggesting potential domain-specific functions in genomic stability and repair mechanisms. This work provides a foundation that will enable future researchers to further dissect the complex roles of DNA2 in replication and repair pathways.

P3, N=102, Completed, Stealth BioTherapeutics Inc. | Active, not recruiting --> Completed

This not only facilitates the cellular apoptosis via the photothermal effect but also improves the efficiency of both Cu+- and Mn2+-based Fenton reactions. The enhanced therapeutic outcome was due to the synergetic combination of PTT and CDT.

APOD is a prognostic biomarker for cervical cancer, and the prognostic model constructed by identified cervical cancer-related genes can successfully distinguish the prognosis of patients with cervical cancer.

These findings explain why DNA2 is essential for cell proliferation and reveal that replication fork processing to restrict recombination is indispensable for avoiding cellular senescence. Stochastic entry into senescence stifles the proliferative potential of cells following the expression of a Seckel syndrome patient-derived DNA2 hypomorph or partial degradation of DNA2, providing a conceptual framework to explain global growth failure in DNA2-linked primordial dwarfism disorders.

Moreover, both the exonuclease and the helicase activities of WRN contribute to MiDAS. Because oncogene-induced replication stress is common in cancers, targeting of WRN or other factors required for MiDAS could facilitate the development of targeted cancer therapies.