Histone proteins (DNA–histone interface) (NCP)

Histone proteins (H2A, H2B, H3, and H4) are the fundamental structural components of the nucleosome, the basic unit of eukaryotic chromatin [1]. The DNA–histone interface is the site where the DNA double helix wraps around the histone octamer, stabilized by numerous electrostatic interactions and hydrogen bonds between the DNA phosphate backbone and histone residues [2]. This interface is essential for compacting the genome and regulating access to genetic information during transcription, replication, and repair [3]. In oncology, this interface is a therapeutic target for drugs like trabectedin and lurbinectedin, which bind to the DNA minor groove and disrupt the stability of the nucleosome, leading to histone eviction and the inhibition of oncogenic transcription factors [4]. Additionally, anthracyclines such as doxorubicin have been shown to induce histone eviction from chromatin, contributing to their cytotoxic and epigenetic effects [5]. Targeting the DNA–histone interface provides a unique mechanism to disrupt oncogenic transcriptional programs and induce apoptosis in rapidly dividing cancer cells [6]. Sources: [1] UniProt (Histone H3.1, P68431). [2] Davey CA, et al. "Solvent structure of the nucleosome core particle at 1.9 A resolution." J Mol Biol. 2002. [3] Luger K, et al. "Crystal structure of the nucleosome core particle at 2.8 A resolution." Nature. 1997. [4] D'Incalci M, et al. "Trabectedin, a drug acting on both cancer cells and the tumour microenvironment." Br J Cancer. 2014. [5] Pang B, et al. "Drug-induced histone eviction from transcriptionally active chromatin." Nat Commun. 2013. [6] Santamaría MG, et al. "Lurbinectedin: A Review in Metastatic Small Cell Lung Cancer." Drugs. 2021.

Other names

Nucleosome core particleHistone octamerChromatin DNA-protein interfaceNucleosomal DNA interface

Disruption of the DNA–histone interface leading to histone eviction, DNA bending, and inhibition of transcription factor binding.