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)