Biology subjects

Minocha, S.

Publications and source records attributed to Minocha, S..

4 recordsLinked to original sources

bioRxiv2026

ZATT/ZNF451 promotes release of stalled TOP2 cleavage complexes

Topoisomerase II (TOP2) resolves DNA topological constraints through a tightly regulated cycle of DNA double-strand cleavage and religation. Nearby DNA damage or chemotherapeutic agents such as etoposide block the DNA religation step, stabilizing TOP2-DNA cleavage complexes (TOP2ccs) at DNA double-strand breaks (DSBs). The SUMO E3 ligase ZATT (ZNF451) has recently emerged as a key effector of TOP2cc repair, but its mechanism of action remains poorly understood. Here, we show that ZATT is sufficient to resolve TOP2ccs independently of TDP2, TOP2 proteolysis, and canonical DSB repair pathways. Using Xenopus egg extracts and biochemical reconstitution, we find that ZATT salvages trapped TOP2 by promoting TOP2 release from its stalled cleavage complex. Structural modeling and targeted mutagenesis in Xenopus egg extracts and human cells identify a highly conserved hydrophobic pocket in the tower domain of TOP2 where the ZATT coiled-coil "hooks on" to promote TOP2cc resolution. Our findings reveal a new strategy to resolve TOP2ccs that bypasses the exposure of dangerous DNA breaks.

molecular biology↗

bioRxiv2025

Unraveling Genomic Signatures of lncRNA Expression in Zebrafish Caudal Fin Regeneration: Bridging Regenerative Potential and Positional Memory.

Zebrafish (Danio rerio) is an essential model organism for tissue regeneration, but the function of long non-coding RNAs (lncRNAs) in tissue regeneration is not well understood. Identifying important regeneration-associated lncRNAs may allow for cross-species applications, improving tissue repair in other organisms. However, few studies and a lack of functional validation complicate our understanding of their mechanistic functions. This research explores novel lncRNAs associated with caudal fin regeneration and positional memory, aiming to identify those that are evolutionarily important across species and may hold universal significance. RNA-seq data deposited in the NCBI database were compared at various important time points (0h post-amputation (hpa), 12 hpa, 1 day post-amputation (dpa), two dpa, three dpa, and seven dpa) and fin parts (proximal, middle, and distal) to uncover major regulatory lncRNAs. Using HISAT2, StringTie, FEELnc, Conservation Analysis and WGCNA (Weighted Gene Co-expression Network Analysis), we found 107 lncRNAs related to regeneration time points and 229 about positional memory during regeneration. Overlapping analysis identified 13 common genomic regions that are complete or partial lncRNAs, indicating a functional connection between regeneration and positional identity and expressed differently in each time point and each position. Additionally, a comparison with regeneration-associated mRNAs revealed that these 13 regions play critical roles in both processes, providing insights into the molecular mechanisms of regenerative precision. Following validation by RT-PCR, the results further suggest that these overlapping regions are differentially expressed across distinct positions within the same tissue, despite a consistent injury pattern. This positional variation in expression may indicate potential roles in both evolutionary adaptation and the regulation of regenerative processes across multiple tissues.

genomics↗

bioRxiv2025

Enhancing salt tolerance in a hybrid poplar (Populus nigra x maximowiczii) through exogenous putrescine application: Growth, physiological, and biochemical responses

IntroductionPutrescine, a polyamine involved in plant growth and stress responses, has shown potential in mitigating abiotic stress effects. However, little is known about the exogenous addition of putrescine regarding salt tolerance in trees. MethodsThis study was conducted to investigate whether exogenous putrescine application via foliar spray enhances growth in a hybrid poplar (Populus nigra x maximowiczii, clone NM6) under a short duration of salt stress. Salt stress was induced by irrigating roots with 100 mM and 200 mM NaCl, followed by foliar spraying of putrescine on several days. Measurement of growth including plant height and stem diameter for each plant were recorded in the greenhouse every 15 days throughout the experiment. Gas exchange, total chlorophyll, carotenoids, soluble sugars and proteins, amino acids, polyamines, and relative water content were analyzed in foliage collected 3, 6, 7, 13, 20, 35 days after treatment. ResultsPutrescine spray on the salt-treated plants caused a significant increase in plant growth. Putrescine application caused a significant increase in fructose, glucose, and galactose in all plants, but putrescine spray had a variable impact on the sucrose content of 100 mM NaCl-treated plants. Based on metabolic responses, plants treated with 100 mM NaCl fared better when sprayed with putrescine than those treated with 200 mM NaCl. DiscussionExogenous application of putrescine mitigated growth inhibition effects of salinity. These finding highlight the potential of putrescine as a practical approach to increase salt tolerance in young poplar trees, with implications for forestry and land reclamation in saline environment.

plant biology↗

bioRxiv2024

Discovery of Novel Long Non-Coding RNAs That May Potentially Play a Role in Zebrafish Brain Regeneration Post Traumatic Injury

Understanding brain regeneration mechanisms is vital for treating neurological conditions. Zebrafish (Danio rerio) are an excellent model due to their genetic similarity to humans and strong regenerative abilities. In this study, we identified novel long non-coding RNAs (lncRNAs) in the regenerating zebrafish brain following traumatic brain injury (TBI). RNA sequencing data of the zebrafish telencephalon from the BioStudies database was analyzed for novel long non-coding RNA expression (lncRNA) at control, one day post-lesion (early wound healing), three days post-lesion (cell proliferation), and 14 days post-lesion (differentiation). We identified 689 potential lncRNAs using HISAT2, StringTie, FEELnc, and PhastCon analysis tools. Principal component analysis (PCA) of identified lncRNAs revealed a distinct expression profile at 1-day post-lesion, indicating their significant role in early wound healing. Weighted Gene Co-expression Network Analysis (WGCNA) identified two modules (brown and turquoise) showing unique expression patterns critical to brain regeneration. Pathway enrichment analysis linked brown module lncRNAs to peptide biosynthesis, cellular amide metabolism, and ribosome biogenesis. In contrast, turquoise module lncRNAs were associated with ion transmembrane transport and cell adhesion pathways. qPCR validation confirmed co-expression patterns of selected lncRNAs and correlated genes, emphasizing their regulatory roles. This study demonstrates that lncRNAs play crucial roles in zebrafish brain regeneration by modulating gene expression during the early wound healing stage. These insights offer potential therapeutic applications of lncRNAs in neuroregenerative medicine.

bioinformatics↗