Cited by 52DNA Repair MechanismsEffects of Radiation ExposureGenomics and Chromatin Dynamics

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

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Di Virgilio, Michela, Ying, Carol Y., Gautier, Jean·2009·DNA Repair

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.

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Crossref · 10.1016/j.dnarep.2009.07.006

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Authors
Di Virgilio, M., Ying, C. Y., & Gautier, J.
Affiliations
Columbia University Irving Medical Center (US)
Corresponding author
Gautier, Jean
Venue
DNA Repair
Publisher
Elsevier BV
Published
2009-11
Volume
8
Issue
11
Pages
1311-1320
ISSN
  • 1568-7856 (ISSN-L)
  • 1568-7864
OpenAlex
W1975192924
Cited by
52
References
84
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 8 · 2013: 4 · 2012: 4
FWCI
1.34
Type
journal article
Language
en
Open access
Locations
  • DNA repair (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders
  • National Cancer Institute (CA 92245, R01CA092245)
  • National Institute of General Medical Sciences (R01GM077495)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
MRN complex, PIKK kinases, DNA double-strand breaks, ATM signaling, Mre11-Rad50-Nbs1, chromatin binding, DNA damage response, checkpoint recovery
MeSH terms
MRE11 Homologue Protein, Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, DNA Repair, DNA-Binding Proteins, Enzyme Activation, Humans, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Kinases, Xenopus laevis, Sequence Alignment, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, Xenopus Proteins, Chromatin Assembly and Disassembly, DNA Repair Enzymes, DNA Breaks, Double-Stranded, Ataxia Telangiectasia Mutated Proteins

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