The human DNA ends proteome uncovers an unexpected entanglement of functional pathways.

Autor:	Berthelot V; Laboratoire de chimie physique, UMR CNRS 8000, University of Paris-Sud, F-91400 Orsay, France., Mouta-Cardoso G; Structure et Instabilité des Génomes, INSERM U1154, UMR CNRS/MNHN 7196, F-75005 Paris, France., Hégarat N; Structure et Instabilité des Génomes, INSERM U1154, UMR CNRS/MNHN 7196, F-75005 Paris, France., Guillonneau F; Plateforme de spectrométrie de masse 3P5, Institut Cochin, F-75014 Paris, France., François JC; Inserm and Sorbonne Universities, UPMC, UMR_S 938, Research Center Saint-Antoine, F-75012 Paris, France., Giovannangeli C; Structure et Instabilité des Génomes, INSERM U1154, UMR CNRS/MNHN 7196, F-75005 Paris, France., Praseuth D; Structure et Instabilité des Génomes, INSERM U1154, UMR CNRS/MNHN 7196, F-75005 Paris, France praseuth@mnhn.fr., Rusconi F; Laboratoire de chimie physique, UMR CNRS 8000, University of Paris-Sud, F-91400 Orsay, France filippo.rusconi@u-psud.fr.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2016 Jun 02; Vol. 44 (10), pp. 4721-33. Date of Electronic Publication: 2016 Feb 25.
DOI:	10.1093/nar/gkw121
Abstrakt:	DNA ends get exposed in cells upon either normal or dysfunctional cellular processes or molecular events. Telomeres need to be protected by the shelterin complex to avoid junctions occurring between chromosomes while failing topoisomerases or clustered DNA damage processing may produce double-strand breaks, thus requiring swift repair to avoid cell death. The rigorous study of the great many proteins involved in the maintenance of DNA integrity is a challenging task because of the innumerous unspecific electrostatic and/or hydrophobic DNA-protein interactions that arise due to the chemical nature of DNA. We devised a technique that discriminates the proteins recruited specifically at DNA ends from those that bind to DNA because of a generic affinity for the double helix. Our study shows that the DNA ends proteome comprises proteins of an unexpectedly wide functional spectrum, ranging from DNA repair to ribosome biogenesis and cytoskeleton, including novel proteins of undocumented function. A global mapping of the identified proteome on published DNA repair protein networks demonstrated the excellent specificity and functional coverage of our purification technique. Finally, the native nucleoproteic complexes that assembled specifically onto DNA ends were shown to be endowed with a highly efficient DNA repair activity. (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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