Nuclear cytochrome c - a mitochondrial visitor regulating damaged chromatin dynamics

Over the past decade, evidence has emerged suggesting a broader role for cytochrome c (Cyt c) in programmed cell death. Recently, we demonstrated the ability of Cyt c to inhibit the nucleosome assembly activity of histone chaperones SET/template-activating factor Iß and NAP1-related protein during D...

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Detalles Bibliográficos
Autores: Díaz-Moreno, Irene, Velázquez-Cruz, Alejandro, Curran-French, Seamus, Díaz-Quintana, Antonio, Rosa, Miguel A. de la
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/169462
Acceso en línea:http://hdl.handle.net/10261/169462
Access Level:acceso abierto
Palabra clave:DNA damage response
Chromatin remodelling
Low-complexity acidic region
Histone chaperone
Cytochrome c
Descripción
Sumario:Over the past decade, evidence has emerged suggesting a broader role for cytochrome c (Cyt c) in programmed cell death. Recently, we demonstrated the ability of Cyt c to inhibit the nucleosome assembly activity of histone chaperones SET/template-activating factor Iß and NAP1-related protein during DNA damage in humans and plants respectively. Here, we hypothesise a dual concentration-dependent function for nuclear Cyt c in response to DNA damage. We propose that low levels of highly cytotoxic DNA lesions - such as double-strand breaks - induce nuclear translocation of Cyt c, leading to the attenuation of nucleosome assembly and, thereby, increasing the time available for DNA repair. If DNA damage persists or is exacerbated, the nuclear Cyt c concentration would exceed a given threshold, causing the haem protein to block DNA remodelling altogether.