DNA stretching in the nucleosome facilitates alkylation by an intercalating antitumour agent.
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.
Davey
Gabriela E
GE
Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
Wu
Bin
B
Dong
Yuancai
Y
Surana
Uttam
U
Davey
Curt A
CA
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*
C522420:2-methyl-1,8-epoxynaphthalimide; D018906:Antineoplastic Agents, Alkylating; D004852:Epoxy Compounds; D007364:Intercalating Agents; D053644:Naphthalimides; D009707:Nucleosomes; D004247:DNA