Biology subjects

Wang, Z.-G.

Publications and source records attributed to Wang, Z.-G..

3 recordsLinked to original sources

bioRxiv2026

The nuclear structural protein NuMA is required for efficient DNA replication by ensuring association of core replication factors to replication forks

DNA replication is a strictly regulated process during cell proliferation to ensure faithful duplication of the genome. Its firing and elongation can be arrested or temporally inhibited in response to a variety of internal and external causes. Inside cells numerous factors including cell cycle checkpoints, protein kinases, and others are involved in the control of this process to maintain genome integrity. Here, we describe that NuMA, a nuclear scaffolding protein, plays an important role in regulating DNA replication. We show that NuMA is present at active replication forks, and its deficiency impairs cell viability, reduces the replication fork speed and increases origin firing, leading to increased level of {gamma}H2AX and the activation of the ATM-CHK2 DNA damage response pathway. Mechanistically, our results show that NuMA depletion reduced the association of multiple key replisome proteins to replication forks, suggesting that NuMA is essential for efficient replisome proteins binding to ongoing forks. Our study uncovers a novel function of NuMA in maintaining genome stability, providing new insights into the important role of nuclear structural proteins in safeguarding DNA replication.

molecular biology↗

bioRxiv2025

SELEX-HTCFQ Platform: Developing DNA Enhancers of ADAR1 to Suppress ZBP1-Dependent Immunopathology

Excessive immune activation drives pathological inflammation through dysregulated ZBP1 signaling, yet this sensor remains crucial for immune surveillance, necessitating targeted therapies that selectively inhibit pathology while preserving protective functions. Here, we developed an innovative SELEX-HTCFQ platform that combines Systematic Evolution of Ligands by Exponential Enrichment (SELEX) with high-throughput competitive fluorescence quenching (HTCFQ) to identify ADAR1-specific enhancers. Capitalizing on ADAR1s natural ability to suppress ZBP1 via competitive Z-nucleic acid binding, this platforms dual assessment of affinity and selectivity identified aptamer A4, a highly specific ADAR1 enhancers demonstrating over 40-fold selectivity over ZBP1. A4 allosterically modulates ADAR1s activity, thereby potentiating its inhibitory effect on ZBP1, which not only mitigates the excessive inflammatory response but also maintains the delicate balance of the immune system. These ADAR1 enhancers represent precision molecular tools for reprogramming Z-nucleic acid sensing, offering a promising therapeutic paradigm for cytokine storm syndromes and necroptosis-driven disorders through selective pathway modulation.

biochemistry↗

bioRxiv2025

Thermodynamic Modeling of mRNA with the Addition of Precipitants

Nucleic acid therapeutics (NATs) have recently emerged as an exciting therapeutic modality for a range of indications, most notably as vaccines for SARS-CoV-2. In many cases, the thermodynamics of a system containing nucleic acids (such as in the downstream purification of mRNA from solution or within the lipid nanoparticle) can significantly influence the properties and efficacy of that system. Consequently, an accurate thermodynamic description of the system is essential for understanding and optimizing that system. In this work, the SAFT-{gamma} Mie equation of state was used to predictively model mRNA solubility. Experimental measurements of the solubility of two different mRNA sequences in various conditions (namely choice of precipitant(s), precipitant concentration, and temperature) were obtained and used to validate the model. Not only was the thermodynamic model able to quantitatively predict the solubility of mRNA in solution under different conditions, it was also able to yield mechanistic insight into the factor driving precipitation, namely the disruption of water-mRNA hydrogen bonding. The developed model can be extended to other mRNA sequences in a range of conditions beyond the experimental data presented in this work.

biophysics↗