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XB-ART-41033
DNA Repair (Amst). November 2, 2009; 8 (11): 1311-20.

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

Di Virgilio M , Ying CY , 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.

PubMed ID: 19709933
PMC ID: PMC2764007
Article link: DNA Repair (Amst).
Grant support: CA92245 NCI NIH HHS , CA92245 NCI NIH HHS , CA92245 NCI NIH HHS , CA92245 NCI NIH HHS , CA92245 NCI NIH HHS , CA92245 NCI NIH HHS , R01 CA092245-08 NCI NIH HHS , R01 CA092245-08 NCI NIH HHS , R01 CA092245-08 NCI NIH HHS , R01 CA092245-08 NCI NIH HHS , R01 CA092245-08 NCI NIH HHS , R01 CA092245-08 NCI NIH HHS , R01 GM077495-02 NIGMS NIH HHS

Genes referenced: atm mre11a nbn rad50
Antibodies referenced:
Morpholinos referenced:

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