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Inspired by the preferential, allosteric binding of RAPTA-T and auranofin to the nucleosome core particle, we describe the design and synthesis of a series of heterobimetallic ruthenium(II)-gold(I) complexes with varying spacer lengths ranging from four to ...
Epigenetics plays an important role in cancer development and progression. Cancer cells hijack the epigenome by modifying the histone protein units responsible for packaging DNA, or by modifying the DNA itself, resulting in changes to chromatin topology an ...
Exploitation of drug-drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with the biological macromolecular landscape. Here we describe a drug-drug synergy mediated ...
Eukaryotic DNA is organized in the form of chromatin whose basic unit is the nucleosome. The four core histones forming the nucleosome, H2A, H2B, H3 and H4 can be highly post-translationally modified, especially on their N-terminal tail protruding from the ...
Through epigenetic mechanisms cells integrate environmental stimuli to fine-tune gene expression levels. Mitochondrial function is essential to provide the intermediate metabolites necessary to generate and modify epigenetic marks in the nucleus, which in ...
Chromatin is the template on which DNA-associated transactions take place in eukaryotic organisms. Nucleosomes consisting of the four histones H2A, H2B, H3 and H4 each organize ~150bp of DNA and constitute a first layer of chromatin. The three-dimensional ...
Designing compounds that bind to the acidic patch of the nucleosome core particle (NCP) is an emerging therapeutic approach that can inhibit the binding of key chromatin factors. Pretreatment of human ovarian carcinoma, A2780, cells with RAPTA-T, an antime ...
The cellular response to DNA damage results in a signaling cascade that primes chromatin for repair. Combinatorial post-translational modifications (PTMs) play a key role in this process by altering the physical properties of chromatin and recruiting downs ...
Dynamic regulation of chromatin, a structure consisting of DNA and histone proteins, is mediated through histone post-translational modifications (PTMs) and effector proteins. HP1a and PRC2 are recruited to repressive PTMs (H3K9me3, H3K27me3) and enable he ...
In eukaryotic cells, DNA is tightly packed in the form chromatin. The basic structure of chromatin is a nucleosome composed of 147 bp DNA wrapped around eight histone proteins; two copies of H2A, H2B, H3 and H4. These histone proteins are decorated with pa ...
