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PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin

Item Type:Article
Title:PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin
Creators Name:Di Virgilio, M. and Ying, C.Y. and Gautier, J.
Abstract:The role of Mre11 phosphorylation in the cellular response to DNA double-strand breaks (DSBs) is not well understood. Here, we show that phosphorylation of Mre11 at SQ/TQ motifs by PIKKs (PI3 Kinase-related Kinases) induces MRN (Mre11-Rad50-Nbs1) complex dissociation from chromatin by reducing Mre11 affinity for DNA. Whereas phosphorylation of Mre11 at these residues is not required for DSB-induced ATM (Ataxia-Telangiectasia mutated) activation, abrogation of Mre11 dephosphorylation impairs ATM signaling. Our study provides a functional characterization of the DNA damage-induced Mre11 phosphorylation, and suggests that MRN inactivation participates in the down-regulation of damage signaling during checkpoint recovery following DSB repair.
Keywords:DNA Damage, MRN Complex, PIKK, Mre11 Phosphorylation, Checkpoint Recovery, Animals, Xenopus laevis
Source:DNA Repair
ISSN:1568-7856
Publisher:Elsevier (The Netherlands)
Volume:8
Number:11
Page Range:1311-1320
Date:2 November 2009
Official Publication:https://doi.org/10.1016/j.dnarep.2009.07.006
PubMed:View item in PubMed

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