title: DNA stretching in the nucleosome facilitates alkylation by an intercalating antitumour agent.
abstract: DNA stretching in the nucleosome core can cause dramatic structural distortions, which may influence compaction and factor recognition in chromatin. We find that the base pair unstacking arising from stretching-induced extreme minor groove kinking near the nucleosome centre creates a hot spot for intercalation and alkylation by a novel anticancer compound. This may have far reaching implications for how chromatin structure can influence binding of intercalator species and indicates potential for the development of site selective DNA-binding agents that target unique conformational features of the nucleosome.
authors.affiliation: Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
authors.forename: Gabriela E
authors.initials: GE
authors.lastname: Davey
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Yuancai
authors.initials: Y
authors.lastname: Dong
authors.forename: Uttam
authors.initials: U
authors.lastname: Surana
authors.forename: Curt A
authors.initials: CA
authors.lastname: Davey
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D018983:DNA Footprinting; D004852:Epoxy Compounds / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry*; D008958:Models, Molecular; D053644:Naphthalimides / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry*
chemical_list: C522420:2-methyl-1,8-epoxynaphthalimide; D018906:Antineoplastic Agents, Alkylating; D004852:Epoxy Compounds; D007364:Intercalating Agents; D053644:Naphthalimides; D009707:Nucleosomes; D004247:DNA