FANCD2 binds MCM proteins and controls replisome function upon activation of s phase checkpoint signaling.

Détails

ID Serval
serval:BIB_CBF02E32F53B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
FANCD2 binds MCM proteins and controls replisome function upon activation of s phase checkpoint signaling.
Périodique
Molecular Cell
Auteur(s)
Lossaint G., Larroque M., Ribeyre C., Bec N., Larroque C., Décaillet C., Gari K., Constantinou A.
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Statut éditorial
Publié
Date de publication
2013
Volume
51
Numéro
5
Pages
678-690
Langue
anglais
Résumé
Proteins disabled in Fanconi anemia (FA) are necessary for the maintenance of genome stability during cell proliferation. Upon replication stress signaling by ATR, the FA core complex monoubiquitinates FANCD2 and FANCI in order to activate DNA repair. Here, we identified FANCD2 and FANCI in a proteomic screen of replisome-associated factors bound to nascent DNA in response to replication arrest. We found that FANCD2 can interact directly with minichromosome maintenance (MCM) proteins. ATR signaling promoted the transient association of endogenous FANCD2 with the MCM2-MCM7 replicative helicase independently of FANCD2 monoubiquitination. FANCD2 was necessary for human primary cells to restrain DNA synthesis in the presence of a reduced pool of nucleotides and prevented the accumulation of single-stranded DNA, the induction of p21, and the entry of cells into senescence. These data reveal that FANCD2 is an effector of ATR signaling implicated in a general replisome surveillance mechanism that is necessary for sustaining cell proliferation and attenuating carcinogenesis.
Mots-clé
Ataxia Telangiectasia Mutated Proteins/metabolism, Cell Aging, Cell Proliferation, Cells, Cultured, DNA Replication, Fanconi Anemia Complementation Group D2 Protein/metabolism, Humans, Minichromosome Maintenance Complex Component 2/genetics, Minichromosome Maintenance Complex Component 2/metabolism, Minichromosome Maintenance Complex Component 7/genetics, Minichromosome Maintenance Complex Component 7/metabolism, S Phase Cell Cycle Checkpoints/physiology, Signal Transduction/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/02/2014 19:22
Dernière modification de la notice
20/08/2019 16:46
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