Artículo del mes
enero 2017

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c

Referencia artículo:
Nucleic Acids Res. (2017) 45 (4): 2150-2165.
En este estudio los autores revelan el papel del citocromo c en la regulación de la reparación de las roturas en el ADN en plantas. Dicha regulación se basa en la inhibición de la chaperona de histonas NRP1, homóloga de la proteína humana SET/TAF-Iβ. La inhibición de la chaperona humana SET/TAF-Iβ por el citocromo c ha sido demostrada por los autores en un trabajo reciente [1]. Los autores proponen la existencia de rutas de regulación del daño en el ADN centradas en el citocromo c, conservadas a lo largo de la evolución. [1] González-Arzola K, et al. (2015) Proc. Natl. Acad. Sci. USA 112: 9908-9913.
Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone chaperone-mediated nucleosome disassembly/reassembly is essential for DNA to be accessible to repair machinery. However, little is known about the specific role and modulation of histone chaperones in the context of DNA damage in plants. Here, the histone chaperone NRP1, which is closely related to human SET/TAF-Iβ was found to exhibit nucleosome assembly activity in vitro and to accumulate in the chromatin of A. thaliana after DNA breaks. In addition, this work establishes that NRP1 binds to cytochrome c, thereby preventing the former from binding to histones. Since NRP1 interacts with cytochrome c at its earmuff domain, that is, its histone-binding domain, cytochrome c thus competes with core histones and hampers the activity of NRP1 as a histone chaperone. Altogether, the results obtained indicate that the underlying molecular mechanisms in nucleosome disassembly/reassembly are highly conserved throughout evolution, as inferred from the similar inhibition of plant NRP1 and human SET/TAF-Iβ by cytochrome c during DNA damage response.
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