Publications by authors named "J M Egly"
The plasticity of cancer cells facilitates their ability to adopt heterogeneous differentiation states, posing a significant challenge to therapeutic interventions. Specific gene expression programs, driven in part by super-enhancers (SEs), underlie cancer cell states. Here we successfully inhibit SE-driven transcription in phenotypically distinct metastatic melanoma cells using next-generation synthetic ecteinascidins.
View Article and Find Full Text PDFLurbinectedin is a selective inhibitor of oncogenic transcription approved for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Preclinical data provide evidence for lurbinectedin exerting its actions in a unique manner that involves oncogenic transcription inhibition, DNA damage, reshaping of the tumor microenvironment, and inducing anticancer immunity. Understanding the mechanism of action (MoA) has facilitated the rational combination of lurbinectedin and anticancer therapies with complementary modes of action, in order to obtain synergistic effects that could potentially lead to improved efficacy.
View Article and Find Full Text PDFThe design and study of rich, bulky phosphorus ligands is a key area of research for homogeneous catalysis. Here, we describe an original strategy using a hydrophosphination reaction to produce phosphines of interest for coordination chemistry and homogenous catalysis. In particular, the phosphine obtained by reacting diphenylphosphine with acenaphthylene (ligand ) gives a ligand that adopts an unusual spatial geometry.
View Article and Find Full Text PDFArticle Synopsis
- Eukaryotic cells have developed sophisticated mechanisms to manage genotoxic stress, which is damage to DNA.
- Cockayne syndrome (CS) is a rare disease caused by mutations in the CSA and CSB genes, initially thought to be solely responsible for DNA repair.
- Recent findings reveal that CSA and CSB are crucial regulators that coordinate DNA repair, transcription, and cell division by ubiquitinating target proteins, highlighting the role of these proteins in the complex nature of CS.
Article Synopsis
- * Lack of EXD2 nuclease impairs recovery of mRNA synthesis and reduces cell survival after UV exposure, while its overexpression (except for a mutated version) restores both RRS and cell viability.
- * The research shows that UV radiation causes EXD2 to move from mitochondria to the nucleus, where it interacts with RNA Polymerase II to degrade freshly synthesized mRNA, aiding transcription restart once DNA repair is completed.