Biology subjects

Jezso, B.

Publications and source records attributed to Jezso, B..

3 recordsLinked to original sources

bioRxiv2026

SSB1 links stress granule regulation to cellular stress responses and renal ischemia-reperfusion injury

Mammalian single-stranded DNA binding protein 1 (SSB1) has been established as an essential component of genome stability in both human cells and mice. Moreover, SSB1 was recently implicated in cytoplasmic stress response by its involvement in Ras GTPase-activating protein-binding protein 1 (G3BP1)-containing cytoplasmic stress granules (SGs) upon various forms of stress. Here, we generated and analyzed human cellular knockout and rodent ischemia-reperfusion (I/R) models to define SSB1s roles in cytoplasmic stress response. Analysis of wild-type as well as SSB1 and G3BP1 knockout human retinal pigment epithelial (RPE-1) cells shows stress-specific incorporation of SSB1 into SGs and a negative regulator role for SSB1 in SG dynamics under sublethal stress conditions. We find that SSB1 knockout measurably increases cellular sensitivity to oxidative stress but does not alter cell proliferation following mild acute stress. Moreover, we detect SSB1 efflux from the nucleus upon stress that is dependent upon the presence of G3BP1 in a stress-specific manner. In addition, using mouse and rat models we observe significant upregulation and robust cytoplasmic granulation of SSB1 upon renal ischemia-reperfusion stress, establishing SSB1s involvement in complex organismal stress response in vivo. Together, our data demonstrate active involvement of SSB1 in cytoplasmic response to cellular stress and acute kidney injury, with implications for targeting stress response functions in cancerous versus non-cancerous contexts. HIGHLIGHTSO_LISSB1 is incorporated into cytoplasmic stress granules and negatively regulates stress granule assembly under sublethal stress conditions C_LIO_LISSB1 shows stress- and G3BP1-dependent nuclear efflux C_LIO_LISSB1 is upregulated and undergoes apical granulation in renal epithelial cells during renal ischemia-reperfusion injury C_LI

cell biology↗

bioRxiv2025

Phase transition drives bacterial single-stranded DNA binding (SSB) protein mobilization during stress response and metabolic adaptation

Single-stranded DNA-binding proteins (SSBs) are ubiquitous factors of genome metabolism, recently recognized for their ability to undergo liquid-liquid phase separation (LLPS). While Escherichia coli SSB (EcSSB) has emerged as a model for bacterial LLPS in vitro, its phase behavior and functional dynamics in vivo have remained largely unexplored. Here, we define the subcellular organization of EcSSB under diverse physiological and stress conditions using super-resolution microscopy coupled with newly developed image analysis tools. We show that EcSSB forms dynamic intracellular assemblies during exponential growth, which partially dissolve in response to DNA damage, oxidative stress, antibiotic exposure, and metabolic adaptation. In contrast, these dynamic reorganizations are attenuated in stationary phase cells. Moreover, we show that EcSSB foci exhibit limited overlap with nucleoid regions under stress-free conditions, whereas stress induction is accompanied by increased DNA association. These in vivo observations are consistent with stress- and growth-phase dependent modulation of EcSSB organization and together with biophysical characterization of EcSSB condensation in vitro suggest a role for LLPS-based dynamic storage and mobilization in response to physiological demands. Our work provides a quantitative framework for analyzing the cellular organization of bacterial proteins and the spatial regulation of genome maintenance factors in changing environments. This knowledge may also support future strategies targeting SSB organization pathways for antimicrobial development.

biochemistry↗

bioRxiv2021

Bloom syndrome helicase contributes to germ line development and longevity in zebrafish

RecQ helicases - also known as the guardians of the genome - play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic pathways. Aside from being conserved from bacteria to vertebrates, their importance is also reflected in the fact that in humans impaired function of multiple RecQ helicase orthologs are known to cause severe sets of problems, including Bloom, Werner or Rothmund-Thomson syndromes. Our aim was to create and characterize a zebrafish (Danio rerio) disease model for Bloom syndrome, a recessive autosomal disorder. In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis and shortened life expectancy brought on by genomic instability. We show that zebrafish blm mutants recapitulate major hallmarks of the human disease, such as shortened lifespan and reduced fertility. Moreover, similarly to other factors involved in DNA repair, some functions of zebrafish Blm bear additional importance in germ line development, and consequently in sex differentiation. Unlike fanc genes and rad51, however, blm appears to effect its function independent of tp53. Therefore, our model will be a valuable tool for further understanding the developmental and molecular attributes of this rare disease, along with providing novel insights into the role of genome maintenance proteins in somatic DNA repair and fertility.

genetics↗