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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???displayArticle.pmcLink??? PMC2764007
???displayArticle.link??? DNA Repair (Amst)
???displayArticle.grants??? [+]
CA92245 NCI NIH HHS , R01 CA092245-08 NCI NIH HHS , R01 GM077495-02 NIGMS NIH HHS , R01 CA092245 NCI NIH HHS , R01 GM077495 NIGMS NIH HHS
Species referenced: Xenopus laevis
Genes referenced: atm mre11 nbn rad50
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