Biology subjects

GEORGE, S.

Publications and source records attributed to GEORGE, S..

3 recordsLinked to original sources

bioRxiv2025

Genomic differentiation of the black-chinned tilapia (Sarotherodon melanotheron) along a fresh-to-hypersaline water gradient

The black-chinned tilapia (Sarotherodon melanotheron) is an African fish species, found in freshwater, brackish, marine and especially hypersaline (up to 110 {per thousand}) habitats in Senegambia. Using 16,786 filtered single nucleotide polymorphism (SNP) markers, we investigated whether it has responded adaptively to this fresh-to-hypersaline water gradient. Significant genetic differentiation between samples was observed (FST = 0.0568, p < 0.01), revealing an interplay between geographic and environmental variation. We focused on a set of outlier SNPs (n = 255; FST = 0.320, p < 0.001) indicative of adaptive variation, 119 of which mapped to annotated genes in the Oreochromis niloticus genome. Significant enrichment was found for physiological pathways relevant to osmosensing and osmoregulation (e.g. inositol phosphate, thyroid hormone synthesis pathways), but also for immune-related pathways that could be activated by ion fluxes (e.g. inflammasome). Some outlier loci mapped to genes that are known to respond to salinity variation in other organisms, including genes found to be differentially expressed in black-chinned tilapia. Adaptive variation along a fresh-to-hypersaline water gradient is well supported in black-chinned tilapia, but its association with climate change specifically induced by hypersalinity deserves further attention particularly in the context of increasing cases of inverted estuaries being reported worldwide.

evolutionary biology↗

bioRxiv2025

Targeting SUV4-20H epigenetic enzymes as therapeutic strategy for enhancing topoisomerase II poisoning in prostate cancer

DNA topoisomerase II (TOP2) plays a crucial role in DNA-associated processes by inducing transient DNA double-strand breaks, making it an important target for DNA-damage stabilizing agents. Commonly used in cancer therapy, these agents are designed to interfere with TOP2 cleavage complexes on chromatin. However, the epigenetic pathways influencing their effectiveness and the resultant cellular responses remain elusive. Here, we combine in vitro as well as in vivo genetic and pharmacological approaches in prostate cancer to demonstrate that inhibiting the histone H4-lysine 20 (H4K20) methyltransferases SUV4-20H1 and SUV4-20H2 induces synthetic lethality when combined with TOP2 poisons, such as etoposide. Remarkably, we show that the loss of SUV4-20H enzymes, which prevents the conversion of H4K20 mono-methylation to higher methylation states, has minimal impact on prostate cancer cell behavior under normal conditions. However, these innocuous epigenetic changes significantly enhances the trapping of TOP2 complex in chromatin and increases DNA damage in response to etoposide. Furthermore, SUV4-20H depletion impairs the repair of TOP2-induced DNA breaks by disrupting the switch from RPA to RAD51 foci at damage sites, leading to extensive cancer cell death and inhibition of prostate tumor growth. Overall, these findings suggest that dual targeting of SUV4-20H and TOP2 activity on chromatin represents a promising therapeutic strategy for prostate cancer, where SUV4-20H2 emerges as a potential marker of aggressive disease and high metastatic risk.

cancer biology↗

bioRxiv2024

Stranded short nascent strand sequencing reveals the topology of eukaryotic DNA replication origins in Trypanosoma brucei.

The universal features that define genomic regions acting as replication origins remain unclear. In this study, we mapped a set of origins in Trypanosoma brucei using stranded short nascent strand sequencing method. Our results showed that DNA replication predominantly initiates in intergenic regions between poly(dA)- and poly(dT)-enriched sequences. G4 structures were detected in the vicinity of some origins and were embedded in poly(dA)-enriched sequences in a strand-specific manner: G4s on the plus strand were located upstream, while those on the minus strand were located downstream of the centre. The origins centres were found to be areas of low nucleosome occupancy, surrounded by regions of high nucleosome occupancy. Furthermore, our results demonstrate that 90% of replication origins overlap with a minor proportion of the previously reported RNA: DNA hybrids. These findings shed new light on the sequence and structural features that define the topology of replication origins in T. brucei. To further characterize replication dynamics at the single-molecule level, we employed DNA combing analysis.

genomics↗