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DNA Repair (Amst). 2009 Nov 2;8(11):1311-20. doi: 10.1016/j.dnarep.2009.07.006. Epub 2009 Aug 25.

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

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  • 1Institute for Cancer Genetics, Department of Genetics and Development, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, 1130 St. Nicholas Avenue, New York, NY 10032, USA.

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.

PMID:
19709933
PMCID:
PMC2764007
DOI:
10.1016/j.dnarep.2009.07.006
[PubMed - indexed for MEDLINE]
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