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Cited by 398

The DOI matches its Crossref record; 232 of the 232 references it cites were found in a registry or an index.

The MRE11–RAD50–NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair

Open access
Syed, Aleem, Tainer, John A.·2018·Annual Review of Biochemistry

Abstract

Genomic instability in disease and its fidelity in health depend on the DNA damage response (DDR), regulated in part from the complex of meiotic recombination 11 homolog 1 (MRE11), ATP-binding cassette–ATPase (RAD50), and phosphopeptide-binding Nijmegen breakage syndrome protein 1 (NBS1). The MRE11–RAD50–NBS1 (MRN) complex forms a multifunctional DDR machine. Within its network assemblies, MRN is the core conductor for the initial and sustained responses to DNA double-strand breaks, stalled replication forks, dysfunctional telomeres, and viral DNA infection. MRN can interfere with cancer therapy and is an attractive target for precision medicine. Its conformations change the paradigm whereby kinases initiate damage sensing. Delineated results reveal kinase activation, posttranslational targeting, functional scaffolding, conformations storing binding energy and enabling access, interactions with hub proteins such as replication protein A (RPA), and distinct networks at DNA breaks and forks. MRN biochemistry provides prototypic insights into how it initiates, implements, and regulates multifunctional responses to genomic stress.

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Crossref · 10.1146/annurev-biochem-062917-012415

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Metadata

Authors
Syed, A., & Tainer, J. A.
Venue
Annual Review of Biochemistry
Published
2018-06-20
Volume
87
Issue
1
Pages
263-294
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
OpenAlex
W2801246231
Cited by
398
References
232
FWCI
3.76
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: The MRE11–RAD50–NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair. https://app.cochat.ai/papers/10.1146/annurev-biochem-062917-012415
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Syed, A., & Tainer, J. A. (2018). The MRE11–RAD50–NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair. Annual Review of Biochemistry. https://doi.org/10.1146/annurev-biochem-062917-012415

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