Wdr5-mediated H3K4 methylation facilitates HSPC development via maintenance of genomic stability in zebrafish

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(12)

Опубликована: Март 20, 2025

During fetal stage, hematopoietic stem and progenitor cells (HSPCs) undergo rapid proliferation with a tight control of genomic stability. Although histone H3 lysine 4 (H3K4) methylation has been reported to stabilize the genome in proliferating cells, its specific role HSPC development remains elusive. In this study, we demonstrated that tryptophan-aspartic acid (WD) repeat protein 5 (Wdr5)-mediated H3K4 is crucial for maintaining stability HSPCs zebrafish embryos. Loss wdr5 led severe reduction pool caudal tissue, accompanied attenuated level evident p53 -dependent apoptosis HSPCs. Mechanistically, Wdr5-mediated maintains by inhibiting formation abnormal R-loops HSPCs, whereas accumulation exacerbates DNA damage. Moreover, absence trimethylation leads an inactivated damage response (DDR) pathway, which deleterious repair Subsequently, found DDR-associated genes, mutL homolog 1 breast ovarian cancer interacting helicase , are important ensure survival, likely stabilizing their genome. summary, these findings reveal essential through R-loop program survival

Язык: Английский

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Metabolic Rewiring in the Face of Genomic Assault: Integrating DNA Damage Response and Cellular Metabolism

Biomolecules, Год журнала: 2025, Номер 15(2), С. 168 - 168

Опубликована: Янв. 23, 2025

The DNA damage response (DDR) and cellular metabolism exhibit a complex, bidirectional relationship crucial for maintaining genomic integrity. Studies across multiple organisms, from yeast to humans, have revealed how cells rewire their in damage, supporting repair processes homeostasis. We discuss immediate metabolic shifts upon detection long-term reprogramming sustained stability, highlighting key signaling pathways participating molecules. Importantly, we examine can conversely induce changes oxidative stress through specific mechanisms, including the histone H2A variant X (H2AX)/ataxia telangiectasia mutated (ATM)/NADPH oxidase 1 (Nox1) pathway repair-specific ROS signatures. review covers organelle-specific responses adaptations associated with different primary focus on human cells. explore implications of this DDR–metabolism crosstalk cancer, aging, neurodegenerative diseases, emerging therapeutic opportunities. By integrating recent findings, provides comprehensive overview intricate interplay between DDR metabolism, offering new perspectives resilience potential avenues intervention.

Язык: Английский

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RSK2-mediated phosphorylation and degradation of UBE2O inhibits hepatocellular carcinoma growth and resistance to radiotherapy

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217558 - 217558

Опубликована: Фев. 1, 2025

Язык: Английский

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TAK-901, a novel EPHA2 inhibitor as a therapeutic strategy against prostate cancer

Cellular Signalling, Год журнала: 2025, Номер 131, С. 111750 - 111750

Опубликована: Март 16, 2025

Prostate cancer is the most common and remains a leading cause of cancer-related deaths among men worldwide. Androgen deprivation therapy continues to be cornerstone treatment for prostate cancer. However, efficacy this treatments often limited, emergence drug resistance tumor recurrence. TAK-901, an inhibitor Aurora kinase B, has been shown inhibit growth both in vitro vivo models. To date, effect TAK-901 on underlying mechanism remain unknown. In study, we found that could proliferation, colony formation migration, while also inducing apoptosis cells. We further demonstrated activates CHK1 signaling pathway, G2/M-phase arrest these Additionally, identified EPHA2 as novel therapeutic target TAK-901. By mutating binding sites between discovered mutations reverse anti-proliferative effects Our study first reveal induces cells inhibits cell by targeting EPHA2. These findings provide valuable insights into mechanisms may develop its applications

Язык: Английский

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Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Март 18, 2025

In the domain of addressing cancer resistance, challenges such as limited effectiveness and treatment resistance remain persistent. Hypoxia is a key feature solid tumors strongly associated with poor prognosis in patients. Another significant portion development acquired drug attributed to tumor stemness. Cancer stem cells (CSCs), small cell subset self-renewal proliferative abilities, are crucial for initiation, metastasis, intra-tumoral heterogeneity. Studies have shown association between hypoxia CSCs context resistance. Recent studies reveal strong link stemness, which together promote survival progression during treatment. This review elucidates interplay CSCs, well their correlation therapeutic drugs. Targeting pivotal genes stemness holds promise novel therapeutics combat

Язык: Английский

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Triple-Action Therapy: Combining Machine Learning, Docking, and Dynamics to Combat BRCA1-Mutated Breast Cancer

Molecular Biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 26, 2024

Язык: Английский

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From biosynthesis to therapeutics: A comprehensive review on varied functions of estrogen and selective estrogen receptor modulators

Journal of Molecular Structure, Год журнала: 2024, Номер 1327, С. 141197 - 141197

Опубликована: Дек. 30, 2024

Язык: Английский

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