Biology subjects

Shamin, A.

Publications and source records attributed to Shamin, A..

3 recordsLinked to original sources

bioRxiv2025

WSB-1 regulates DNA repair and the response to DNA damage response inhibitors in breast cancer

Tumour hypoxia is a poor prognostic factor and linked with metastatic spread and treatment resistance in most solid tumours, including breast cancer. We previously showed hypoxia-regulated E3 ligase WSB-1s association with poor prognosis in breast cancer. Here, we evaluated the role of WSB-1 in DNA repair regulation in breast cancer, and whether these phenotypes can be exploited therapeutically. WSB-1 knockdown led to transcriptome-wide DNA repair factor upregulation, including homologous recombination (HR) factors BRCA1and RAD51. Reciprocally, WSB-1 overexpression led to downregulation of these repair factors and decreased DNA repair capacity. Patient gene expression datasets analyses also showed an inverse correlation between WSB1 expression vs DNA repair and HR pathways. HR-deficient cancers, including BRCA1/2-deficient breast cancers, are extremely sensitive to PARP inhibitors, a phenotype described as BRCAness. We therefore hypothesised if high WSB-1 expression could be similarly exploited therapeutically. WSB-1 overexpression alone radiosensitised cells and led to increased Olaparib (PARP inhibitor) and Berzosertib (ATR inhibitor) sensitivity in vitro. Our study indicates that WSB-1 expression in breast cancer is associated with modulation of HR factor expression, and we propose that elevated WSB-1 expression could be considered as a potential BRCAness biomarker and promote increased sensitivity to DNA repair targeted therapy in these patients.

cancer biology↗

bioRxiv2025

Fungal susceptibility and early flowering in pennycress (Thlaspi arvense) are conferred by naturally occurring mutations in histone demethylase Jumonji 14

Pennycress (Thlaspi arvense) is a winter oilseed domesticated recently to be incorporated as an intermediate crop between the existing cropping systems of the US Midwest. We show that a natural accession of pennycress, 2032, is more susceptible to the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Alternaria japonica than the reference pennycress accession MN106. A previously identified marker associated with early flowering and maturity in pennycress was found to be present in a gene homologous to Arabidopsis Jumonji 14 (JMJ14). It has been reported that AtJMJ14 promotes disease resistance and represses flowering, and greenhouse studies of breeding populations confirmed this phenomenon in pennycress. Plants with the 2032 TaJMJ14 allele were more susceptible to fungi and flowered early. CRISPR-Cas9 editing was used to generate additional TaJMJ14 alleles. A 9-base pair deletion in the 6th exon of TaJMJ14 showed trends of early flowering and S. sclerotiorum susceptibility, whereas a complete loss-of-function allele led to infertility. We further investigated the transcriptomes of MN106 and 2032 plants in the early stages of S. sclerotiorum and A. japonica infection to identify potential resistance and susceptibility genes. Differences in the expression of pathogen-associated molecular pattern-triggered immunity (PTI)-associated genes led us to discover that 2032 plants have defects in elicitor-triggered oxidative bursts. The transcriptional responses unique to each accession lay a foundation for future gene-editing and breeding approaches to keep the beneficial early flowering phenotype conferred by 2032 but uncouple it from disease susceptibility.

plant biology↗

bioRxiv2019

Heating quinoa shoots results in yield loss by inhibiting fruit production and delaying maturity

Increasing global temperatures and a growing world population create the need to develop crop varieties that yield more in warmer climates. There is growing interest in expanding quinoa cultivation, because of quinoas ability to produce nutritious grain in poor soils, with little water and at high salinity. However, the main limitation to expanding quinoa cultivation is quinoas susceptibility to temperatures above ~32{degrees}C. This study investigates the phenotypes, genes, and mechanisms that may affect quinoa seed yield at high temperatures. By using a differential heating system where only roots or only shoots were heated, quinoa yield losses were attributed to shoot heating. Plants with heated shoots lost 60% to 85% yield as compared to control. Yield losses were due to lower fruit production, which lowered the number of seeds produced per plant. Further, plants with heated shoots had delayed maturity and more non-reproductive shoot biomass, while plants with both heated roots and heated shoots produced more yield from panicles that escaped heat than control. This suggests that quinoa uses a type of avoidance strategy to survive heat. Gene expression analysis identified transcription factors differentially expressed in plants with heated shoots and low yield that had been previously associated with flower development and flower opening. Interestingly, in plants with heated shoots, flowers stayed closed during the day while control flowers were open. Although a closed flower may protect floral structures, this could also cause yield losses by limiting pollen dispersal, which is necessary to produce fruit in quinoas mostly female flowers.\n\nSignificance StatementThis study provides evidence that heating quinoa during flowering results in seed yield loss by lowering fruit production. Plants with low yield after heat treatment also matured more slowly, suggesting that quinoa may use a type of avoidance strategy to survive heat stress conditions. Genes differentially expressed under heat include genes involved in flower development and flower opening.

plant biology↗