Epigenetic orchestration of the DNA damage response: Insights into the regulatory mechanisms.

The DNA damage response (DDR) is a critical cellular mechanism that safeguards genome integrity and prevents the accumulation of harmful DNA lesions. Increasing evidence highlights the intersection between DDR signaling and epigenetic regulation, offering profound insights into various aspects of cellular function including oncogenesis. This comprehensive review explores the intricate relationship between the epigenetic modifications and DDR activation, with a specific focus on the impact of viral infections.

UBR7 E3 Ligase Suppresses Interferon-β Mediated Immune Signaling by Targeting Sp110 in Hepatitis B Virus-Induced Hepatocellular Carcinoma.

A newly discovered E3 ubiquitin ligase, UBR7, plays a crucial role in histone H2BK120 monoubiquitination. Here, we report a novel function of UBR7 in promoting hepatitis B virus (HBV) pathogenesis, which further leads to HBV-induced hepatocellular carcinoma (HCC). Transcriptomics analysis from HCC patients revealed the deregulation of UBR7 in cancer.

UBR7 in concert with EZH2 inhibits the TGF-β signaling leading to extracellular matrix remodeling.

The intricate interplay between resident cells and the extracellular matrix (ECM) profoundly influences cancer progression. In triple-negative breast cancer (TNBC), ECM architecture evolves due to the enrichment of lysyl oxidase, fibronectin, and collagen, promoting distant metastasis. Here we uncover a pivotal transcription regulatory mechanism involving the epigenetic regulator UBR7 and histone methyltransferase EZH2 in regulating transforming growth factor (TGF)-β/Smad signaling, affecting the expression of ECM genes.

A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance.

Epigenetic regulation established during development to maintain patterns of transcriptional expression and silencing for metabolism and other fundamental cell processes can be reprogrammed in cancer, providing a molecular mechanism for persistent alterations in phenotype. Metabolic deregulation and reprogramming are thus an emerging hallmark of cancer with opportunities for molecular classification as a critical preliminary step for precision therapeutic intervention. Yet, acquisition of therapy resistance against most conventional treatment regimens coupled with tumor relapse, continue to pose unsolved problems for precision healthcare, as exemplified in breast cancer where existing data informs both cancer genotype and phenotype.

Electrochemical labelling of hydroxyindoles with chemoselectivity for site-specific protein bioconjugation.

Electrochemistry has recently emerged as a powerful approach in small-molecule synthesis owing to its numerous attractive features, including precise control over the fundamental reaction parameters, mild reaction conditions and innate scalability. Even though these advantages also make it an attractive strategy for chemoselective modification of complex biomolecules such as proteins, such applications remain poorly developed. Here we report an electrochemically promoted coupling reaction between 5-hydroxytryptophan (5HTP) and simple aromatic amines-electrochemical labelling of hydroxyindoles with chemoselectivity (eCLIC)-that enables site-specific labelling of full-length proteins under mild conditions.

Lnc-ing epigenetic mechanisms with autophagy and cancer drug resistance.

Long noncoding RNAs (lncRNAs) comprise a diverse class of RNA molecules that regulate various physiological processes and have been reported to be involved in several human pathologies ranging from neurodegenerative disease to cancer. Therapeutic resistance is a major hurdle for cancer treatment. Over the past decade, several studies has emerged on the role of lncRNAs in cancer drug resistance and many trials have been conducted employing them.

Conceptual advances in nucleophilic organophosphine-promoted transformations.

Catalysis by trivalent nucleophilic organophosphines has emerged as an essential tool in organic synthesis. Several new organic transformations promoted by phosphines substantiate and complement the existing synthetic chemistry tools. Mere design of the substrate and reagent combinations has introduced new modes of reactivity patterns, which are otherwise difficult to achieve.

Autophagy in Cancer: A Metabolic Perspective.

Autophagy is an intracellular catabolic degradative process in which damaged cellular organelles, unwanted proteins and different cytoplasmic components get recycled to maintain cellular homeostasis or metabolic balance. During autophagy, a double membrane vesicle is formed to engulf these cytosolic materials and fuse to lysosomes wherein the entire cargo degrades to be used again. Because of this unique recycling ability of cells, autophagy is a universal stress response mechanism.

Epigenetic regulation of Fructose-1,6-bisphosphatase 1 by host transcription factor Speckled 110 kDa during hepatitis B virus infection.

Hepatitis B virus (HBV) is the leading cause of liver disease ranging from acute and chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Studies have revealed that HBV infection broadly reprogrammes the host cellular metabolic processes for viral pathogenesis. Previous reports have shown that glycolysis and gluconeogenesis are among the most deregulated pathways during HBV infection.

Phosphine-Catalyzed Intramolecular Vinylogous Aldol Reaction of α-Substituted Enones.

We demonstrate the first phosphine-catalyzed intramolecular vinylogous aldol reaction (IVAR) of α-substituted enones. This strategy provides access to various pentannulated (hetero)arenes and dibenzocycloheptanones incorporated with two contiguous stereocenters, one of which is an all-carbon quaternary center. The scope of this work is further broadened through elaborations of the IVAR adducts to (i) benzannulated nine-membered carbocyclic systems, (ii) interesting classes of 1,3-dienes, 1,3,5-trienes, and 1-yn-3,5-dienes, and (iii) the analogs of echinolactone D and russujaponol F.

Stress Responses as Master Keys to Epigenomic Changes in Transcriptome and Metabolome for Cancer Etiology and Therapeutics.

From initiation through progression, cancer cells are subjected to a magnitude of endogenous and exogenous stresses, which aid in their neoplastic transformation. Exposure to these classes of stress induces imbalance in cellular homeostasis and, in response, cancer cells employ informative adaptive mechanisms to rebalance biochemical processes that facilitate survival and maintain their existence. Different kinds of stress stimuli trigger epigenetic alterations in cancer cells, which leads to changes in their transcriptome and metabolome, ultimately resulting in suppression of growth inhibition or induction of apoptosis.

Annulative Morita-Baylis-Hillman reaction to synthesise chiral dibenzocycloheptanes.

We describe the first metal-free and organocatalytic strategy to access highly functionalised dibenzocycloheptanes a phosphine-promoted annulative Morita-Baylis-Hillman (MBH) reaction. The method is manipulated to access to chiral dibenzocycloheptanes as well. This work represents a rare entry for the construction of seven-membered carbocycles the MBH route.

Organocatalytic Strategies for the Synthesis of Cyclopenta-Fused Arenes and Heteroarenes.

Cyclopentanoids are omnipresent in natural products and pharmaceutically relevant compounds. Among them, cyclopenta-fused arenes and heteroarenes possess impressive biological properties and play significant role in materials science. Consequently, several notable methods have been developed for their synthesis over the years.