DNA stretching in the nucleosome facilitates alkylation by an intercalating antitumour agent |
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| Authors: | Gabriela E Davey Bin Wu Yuancai Dong Uttam Surana Curt A Davey |
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| Institution: | 1.Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, 2.Institute of Chemical and Engineering Sciences, (A*STAR) Agency for Science, Technology and Research, 1 Pesek Road, Jurong Island, Singapore 627833 and 3.Institute of Molecular and Cell Biology, (A*STAR) Agency for Science, Technology and Research, Proteos, 61 Biopolis Drive, Singapore 138673 |
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| 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. |
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