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XB-ART-41033
DNA Repair (Amst) 2009 Nov 02;811:1311-20. doi: 10.1016/j.dnarep.2009.07.006.
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PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin.

Di Virgilio M, Ying CY, Gautier J.


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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.

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Species referenced: Xenopus laevis
Genes referenced: atm mre11 nbn rad50

References [+] :
Abraham, PI 3-kinase related kinases: 'big' players in stress-induced signaling pathways. 2004, Pubmed