Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iß by cytochrome c
Resumen: 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 re- gulators 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 chap- erone SET/TAF-Iß 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-Iß to core histones, thereby locking its histone-binding domains and inhibiting its nucle- osome assembly activity. In addition, we have used NMR spectros- copy, 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-Iß. Overall, these findings estab- lish a framework for understanding the molecular basis of cyto- chrome c-mediated blocking of SET/TAF-Iß, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iß’s histone chaperone activity.
Idioma: Inglés
DOI: 10.1073/pnas.1508040112
Año: 2015
Publicado en: Proceedings of the National Academy of Sciences 112, 32 (2015), 9908-9913
ISSN: 0027-8424

Factor impacto JCR: 9.423 (2015)
Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 4 / 62 = 0.065 (2015) - Q1 - T1
Factor impacto SCIMAGO: 6.814 - Multidisciplinary (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2012-31670
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2012-32824
Tipo y forma: Article (Published version)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)

Creative Commons You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes.


Exportado de SIDERAL (2021-01-21-11:15:19)

Este artículo se encuentra en las siguientes colecciones:
Articles



 Record created 2016-07-25, last modified 2021-01-21


Versión publicada:
 PDF
Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)