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|Title:||Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation||Authors:||Davey, Gabriela Elzbieta
Murray, Benjamin S.
Dyson, Paul J.
Davey, Curtis Alexander
|Issue Date:||2017||Source:||Davey, G. E., Adhireksan, Z., Ma, Z., Riedel, T., Sharma, D., Padavattan, S., et al. (2017). Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation. Nature Communications, 8(1), 1575-.||Series/Report no.:||Nature Communications||Abstract:||The ‘acidic patch’ is a highly electronegative cleft on the histone H2A–H2B dimer in the nucleosome. It is a fundamental motif for protein binding and chromatin dynamics, but the cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize a family of binuclear ruthenium compounds that selectively target the nucleosome acidic patch, generating intra-nucleosomal H2A-H2B cross-links as well as inter-nucleosomal cross-links. In contrast to cisplatin or the progenitor RAPTA-C anticancer drugs, the binuclear agents neither arrest specific cell cycle phases nor elicit DNA damage response, but rather induce an irreversible, anomalous state of condensed chromatin that ultimately results in apoptosis. In vitro, the compounds induce misfolding of chromatin fibre and block the binding of the regulator of chromatin condensation 1 (RCC1) acidic patch-binding protein. This family of chromatin-modifying molecules has potential for applications in drug development and as tools for chromatin research.||URI:||https://hdl.handle.net/10356/89472
|ISSN:||2041-1723||DOI:||10.1038/s41467-017-01680-4||Rights:||© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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