PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin
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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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Mre11 phosphorylation by ATM/ATR may participate in checkpoint recovery after double-strand break repair.
“It has been demonstrated that Mre11 phosphorylation by ATM/ATR may participate in the checkpoint recovery following DSB repair [176].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [176]
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- Authors
- Di Virgilio, M., Ying, C. Y., & Gautier, J.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Gautier, Jean
- ORCID
- 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
- PMC
- PMC2764007
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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