MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair.

Détails

ID Serval
serval:BIB_FC743A0ACC8B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair.
Périodique
The EMBO journal
Auteur⸱e⸱s
Roques C., Coulombe Y., Delannoy M., Vignard J., Grossi S., Brodeur I., Rodrigue A., Gautier J., Stasiak A.Z., Stasiak A., Constantinou A., Masson J.Y.
ISSN
1460-2075[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
28
Numéro
16
Pages
2400-2413
Langue
anglais
Résumé
Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading to repair of interstrand cross-links. It was reported earlier that FANCD2 co-localizes with NBS1. However, the functional connection between FANCD2 and MRE11 is poorly understood. In this study, we show that inhibition of MRE11, NBS1 or RAD50 leads to a destabilization of FANCD2. FANCD2 accumulated from mid-S to G2 phase within sites containing single-stranded DNA (ssDNA) intermediates, or at sites of DNA damage, such as those created by restriction endonucleases and laser irradiation. Purified FANCD2, a ring-like particle by electron microscopy, preferentially bound ssDNA over various DNA substrates. Inhibition of MRE11 nuclease activity by Mirin decreased the number of FANCD2 foci formed in vivo. We propose that FANCD2 binds to ssDNA arising from MRE11-processed DNA double-strand breaks. Our data establish MRN as a crucial regulator of FANCD2 stability and function in the DNA damage response.
Mots-clé
Cell Cycle Proteins/genetics, Cell Cycle Proteins/metabolism, DNA Breaks, Double-Stranded, DNA Repair, DNA Repair Enzymes/genetics, DNA Repair Enzymes/metabolism, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Down-Regulation, Fanconi Anemia Complementation Group D2 Protein/analysis, Fanconi Anemia Complementation Group D2 Protein/genetics, Hela Cells, Humans, Microscopy, Electron, Nuclear Proteins/genetics, Nuclear Proteins/metabolism, Protein Binding, Protein Stability, RNA, Small Interfering/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/11/2009 15:14
Dernière modification de la notice
20/08/2019 16:27
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