Nucleosome (DNA-histone complex)

The DNA-histone complex, fundamentally organized as the nucleosome, serves as the primary structural unit for packaging eukaryotic DNA into chromatin. It consists of a histone octamer—comprising two copies each of histones H2A, H2B, H3, and H4—around which approximately 147 base pairs of DNA are wrapped [1, 2]. Beyond its structural role, the complex is a dynamic regulator of genomic access, influencing transcription, DNA replication, and repair through epigenetic modifications and chromatin remodeling [3]. In clinical contexts, the stability and modification state of this complex are frequently altered; for instance, oncohistone mutations can drive oncogenesis by disrupting normal gene expression patterns [3]. Furthermore, nucleosomes released into the bloodstream during cell death serve as potent autoantigens in systemic lupus erythematosus and as diagnostic biomarkers in various cancers [4, 7]. Therapeutic agents such as anthracyclines target this complex by intercalating into the DNA, which can trigger the eviction of histones and subsequent cell death in rapidly dividing malignant cells [5]. Platinum-based drugs also interact with this complex by forming DNA adducts that are processed differently depending on their position within the nucleosome [6]. [1] Luger, K., et al. (1997). Nature, 389(6648), 251-260. [2] Kornberg, R. D. (1974). Science, 184(4139), 868-871. [3] Allis, C. D., & Jenuwein, T. (2016). Nature Reviews Genetics, 17(8), 487-500. [4] Rekvig, O. P. (2015). Frontiers in Immunology, 6, 427. [5] Pang, B., et al. (2013). Nature Communications, 4, 1908. [6] Zhu, G., et al. (2012). Nature, 489(7416), 447-451. [7] Volckmar, A. L., et al. (2018). Genes, Chromosomes and Cancer, 57(3), 123-139.

Other names

Chromatin unitNucleosome core particleDNA-histone octamerHistone-DNA complex

Drugs interact with the DNA-histone complex through DNA intercalation, which can lead to histone eviction and chromatin destabilization, or by forming covalent DNA adducts that impede transcription and replication within the nucleosomal structure.