Biology subjects

Borsos, B. N.

Publications and source records attributed to Borsos, B. N..

3 recordsLinked to original sources

bioRxiv2025

The Cause of Most Common Antler Abnormality is Not a Fracture But an Osteomyelitis Like Disease the Pedunculitis Chronica Deformans

Climate change is increasing the incidence of certain diseases in wildlife, offering a deeper understanding of their underlying causes. Traditionally, the most common antler abnormalities have been attributed to trauma, based on their morphology. However, this explanation does not account for the epidemic-like spread of abnormalities in specific regions, suggesting that they might be a previously undescribed aspect of this anomaly. In fallow deer (Dama dama), using advanced medical diagnostic tools, we identified an osteomyelitis-like condition, Pedunculitis Chronica Deformans (PCD) which is also observed in other Cervidae. The incidence of this disease shows a strong correlation with the production of mycotoxins by molds that are becoming more prevalent with global warming. Mycotoxins can inhibit wound healing through scar formation after the antlers are cast, leading to the development of PCD. In this report we characterize PCD pathomorphology and introduce a scoring system to differentiate it from other deformities. Moreover, we argue that the most common anomalies such as fractures, antler losses, fatal meningoencephalitis and brain abscesses are complications of PCD. Our research underscores the potential of antlers to serve as biomarkers for mycotoxin exposure.

zoology↗

bioRxiv2023

Cytoplasmic Aggregation of RPB1 Predicts Failure of Neoadjuvant Chemotherapy

We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such event, we followed cytoplasmic aggregation of RPB1, the aggregation prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining - from biopsy samples taken before treatment - the effectiveness of neoadjuvant chemotherapy.

cancer biology↗

bioRxiv2021

Old players in new posts: the role of P53, ATM and DNAPK in DNA damage-related ubiquitylation-dependent removal of S2P RNAPII

DNA double-strand breaks are the most deleterious lesions for the cells, therefore understanding the macromolecular interactions in the DNA repair-related mechanisms is essential. DNA damage triggers transcription silencing at the damage site, leading to the removal of the elongating RNA polymerase II (S2P RNAPII) from this locus, which provides accessibility for the repair factors to the lesion. Ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNAPK) are the two main regulatory kinases of homologous recombination and non-homologous end joining, respectively. Although these kinases are involved in the activation of different repair pathways, they have common target proteins, such as P53. We previously demonstrated that following transcription block, P53 plays a pivotal role in transcription elongation process by interacting with S2P RNAPII. In the current study, we reveal that P53, ATM and DNAPK are involved in the fine-tune regulation of the ubiquitin-proteasome system-related degradation of S2P RNAPII. However, they act differently in this process: P53 delays the removal of S2P RNAPII, while ATM and DNAPK participate in the activation of members of E3 ligase complexes involved in the ubiquitylation of S2P RNAPII. We also demonstrate that WW domain-containing protein 2 (WWP2) and Cullin-3 (CUL3) are interaction partners of S2P RNAPII, thus forming a complex with the transcribing RNAPII complex. Simple SummaryTo ensure the proper repair following DNA double-strand breaks, the eviction of the arrested elongating RNA polymerase II (S2P RNAPII) is required. Here, we report an emerging role of P53, Ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNAPK) in the ubiquitin-proteasome system-dependent removal of S2P RNAPII. We also identified interactions between S2P RNAPII and WW domain-containing protein 2 (WWP2) or Cullin-3 (CUL3) (members of E3 ligase complexes), which are involved in the ubiquitylation of S2P RNAPII following DNA damage. Furthermore, the RNAPII-E3 ligase complex interactions are mediated by P53, ATM and DNAPK, which suggests potential participation of all three proteins in the effective resolution of transcription block at the damage site. Altogether, our results provide a better comprehension of the molecular background of transcription elongation block-related DNA repair processes and highlight an indispensable function of P53, ATM and DNAPK in these mechanisms.

molecular biology↗