Structural highlights
Function
H32_XENLA Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Publication Abstract from PubMed
Understanding how small molecules interact with DNA is essential since it underlies a multitude of pathological conditions and therapeutic interventions. Many different intercalator compounds have been studied because of their activity as mutagens or drugs, but little is known regarding their interaction with nucleosomes, the protein-packaged form of DNA in cells. Here, using crystallographic methods and molecular dynamics simulations, we discovered that adducts formed by [(eta6 -THA)Ru(ethylenediamine)Cl][PF6 ] (THA=5,8,9,10-tetrahydroanthracene; RAED-THA-Cl[PF6 ]) in the nucleosome comprise a novel one-stranded intercalation and DNA distortion mode. Conversely, the THA group in fact remains solvent exposed and does not disrupt base stacking in RAED-THA adducts on B-form DNA. This newly observed DNA binding mode and topology dependence may actually be prevalent and should be considered when studying covalently binding intercalating compounds.
An Organometallic Compound which Exhibits a DNA Topology-Dependent One-Stranded Intercalation Mode.,Ma Z, Palermo G, Adhireksan Z, Murray BS, von Erlach T, Dyson PJ, Rothlisberger U, Davey CA Angew Chem Int Ed Engl. 2016 May 17. doi: 10.1002/anie.201602145. PMID:27184539[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ma Z, Palermo G, Adhireksan Z, Murray BS, von Erlach T, Dyson PJ, Rothlisberger U, Davey CA. An Organometallic Compound which Exhibits a DNA Topology-Dependent One-Stranded Intercalation Mode. Angew Chem Int Ed Engl. 2016 May 17. doi: 10.1002/anie.201602145. PMID:27184539 doi:http://dx.doi.org/10.1002/anie.201602145
