Article
Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c
Author/s | González Arzola, Katiuska
Díaz Moreno, Irene Cano González, Ana María Díaz Quintana, Antonio Jesús Velázquez Campoy, Adrián Moreno Beltrán, José Blas López Rivas, Abelardo Rosa Acosta, Miguel Ángel de la |
Department | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Publication Date | 2015 |
Deposit Date | 2018-01-12 |
Published in |
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Abstract | Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key regulators of damaged chromatin’s ... Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key regulators of damaged chromatin’s transcriptional activity. However, understanding how chaperones are modulated during DNA damage response is still challenging. This study reveals that the histone chaperone SET/TAF-Iβ interacts with cytochrome c following DNA damage. Specifically, cytochrome c is shown to be translocated into cell nuclei upon induction of DNA damage, but not upon stimulation of the death receptor or stress-induced pathways. Cytochrome c was found to competitively hinder binding of SET/TAF-Iβ to core histones, thereby locking its histone-binding domains and inhibiting its nucleosome assembly activity. In addition, we have used NMR spectroscopy, calorimetry, mutagenesis, and molecular docking to provide an insight into the structural features of the formation of the complex between cytochrome c and SET/TAF-Iβ. Overall, these findings establish a framework for understanding the molecular basis of cytochrome c-mediated blocking of SET/TAF-Iβ, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iβ’s histone chaperone activity. |
Funding agencies | Ministerio de Economía y Competitividad (MINECO). España |
Project ID. | FU2012-31670
BFU2010-19451 BFU2013- 47064-P SAF2012-32824 RD12/0036/002 |
Citation | González Arzola, K., Díaz Moreno, I., Cano González, A.M., Díaz Quintana, A.J., Velázquez Campoy, A., Moreno Beltrán, B.,...,Rosa Acosta, M.Á.d.l. (2015). Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c. Proceedings of the National Academy of Sciences, 112 (32), 9908-9913. |
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