Cited by 399DNA Repair MechanismsGenomics and Chromatin DynamicsDNA and Nucleic Acid Chemistry

Mre11–Rad50–Nbs1 is a keystone complex connecting DNA repair machinery, double-strand break signaling, and the chromatin templateThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

Williams, R. Scott, Williams, Jessica S., Tainer, John A.·2007·Biochemistry and Cell Biology

Abstract

The Mre11–Rad50–Nbs1 (MRN) complex is providing paradigm-shifting results of exceptional biomedical interest. MRN is among the earliest respondents to DNA double-strand breaks (DSBs), and MRN mutations cause the human cancer predisposition diseases Nijmegen breakage syndrome and ataxia telangiectasia-like disorder (ATLD). MRN’s 3-protein multidomain composition promotes its central architectural, structural, enzymatic, sensing, and signaling functions in DSB responses. To organize the MRN complex, the Mre11 exonuclease directly binds Nbs1, DNA, and Rad50. Rad50, a structural maintenance of chromosome (SMC) related protein, employs its ATP-binding cassette (ABC) ATPase, Zn hook, and coiled coils to bridge DSBs and facilitate DNA end processing by Mre11. Contributing to MRN regulatory roles, Nbs1 harbors N-terminal phosphopeptide interacting FHA and BRCT domains, as well as C-terminal ataxia telangiectasia mutated (ATM) kinase and Mre11 interaction domains. Current emerging structural and biological evidence suggests that MRN has 3 coupled critical roles in DSB sensing, stabilization, signaling, and effector scaffolding: (1) expeditious establishment of protein – nucleic acid tethering scaffolds for the recognition and stabilization of DSBs; (2) initiation of DSB sensing, cell-cycle checkpoint signaling cascades, and establishment of epigenetic marks via the ATM kinase; and (3) functional regulation of chromatin remodeling in the vicinity of a DSB.

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Crossref · 10.1139/o07-069

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Authors
Williams, R. S., Williams, J. S., & Tainer, J. A.
Affiliations
Scripps Research Institute (US)
Venue
Biochemistry and Cell Biology
Published
2007-08
Volume
85
Issue
4
Pages
509-520
ISSN
  • 0829-8211 (ISSN-L)
  • 1208-6002
OpenAlex
W2161560609
Cited by
399
References
119
Citations by year
2026: 8 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 8 · 2021: 13 · 2020: 17 · 2019: 15 · 2018: 22 · 2017: 22 · 2016: 18 · 2015: 19 · 2014: 27 · 2013: 24 · 2012: 27
FWCI
3.00
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry and Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA92584, CA117638, R01CA117638, P01CA092584)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
Mre11-Rad50-Nbs1 complex, MRN complex, DNA double-strand break repair, Nijmegen breakage syndrome, ataxia-telangiectasia-like disorder, RAD50, NBS1, ATM kinase, DNA end processing, chromatin remodeling, epigenetic modifications
MeSH terms
MRE11 Homologue Protein, Chromatin, DNA, DNA Repair, DNA-Binding Proteins, Enzyme Activation, Humans, Models, Molecular, Nuclear Proteins, Protein Conformation, Signal Transduction, Protein Serine-Threonine Kinases, Acid Anhydride Hydrolases, Cell Cycle Proteins, Tumor Suppressor Proteins, DNA Repair Enzymes, Macromolecular Substances, DNA Breaks, Double-Stranded, Ataxia Telangiectasia Mutated Proteins

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