Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex
Open accessAbstract
The Nijmegen breakage syndrome gene product (Nbs1) was shown recently to associate in vivo with the Mre11 and Rad50 proteins, which play pivotal roles in eukaryotic DNA double-strand break repair, meiotic recombination, and telomere maintenance. We show in this work that the triple complex of recombinant Nbs1, Mre11, and Rad50 proteins binds cooperatively to DNA and forms a distinct protein-DNA species. The Mre11/Rad50/Nbs1 complex displays several enzymatic activities that are not seen without Nbs1, including partial unwinding of a DNA duplex and efficient cleavage of fully paired hairpins. Unwinding and hairpin cleavage are both increased by the presence of ATP. On nonhairpin DNA ends, ATP controls a switch in endonuclease specificity that allows Mre11/Rad50/Nbs1 to cleave a 3'-protruding strand at a double-/single-strand transition. Mutational analysis demonstrates that Rad50 is responsible for ATP binding by the complex, but the ATP-dependent activities are expressed only with Nbs1 present.
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A multimeric complex, including Mre11, Nbs1, Rad50, and other proteins, is necessary to repair broken DNA.
“Therefore, a multimeric complex, including Mre11, Nbs1, Rad50, and other proteins, is necessary to repair broken DNA.”
From Mdm2 Binds to Nbs1 at Sites of DNA Damage and Regulates Double Strand Break Repair (2005) · cites this paper as [2]
In “A model for the role of M/R/N in double-strand break repair” (page unavailable), the paper identifies an Mre11/Rad50/Nbs1 complex involved in repairing double-strand breaks and reports that the Mre11 complex is necessary for joining plasmid ends in vivo. It describes other proteins as factors the complex may recruit or assemble at DNA ends, not as established members of a larger complex necessary for all broken-DNA repair. (LLM, conf=0.84)
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- Authors
- Paull, T. T., & Gellert, M.
- Affiliations
- National Institutes of Health (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-05-15
- Volume
- 13
- Issue
- 10
- Pages
- 1276-1288
- ISSN
- 0890-9369 (ISSN-L)
- PMC
- PMC316715
- OpenAlex
- W2123909581
- Cited by
- 551
- References
- 67
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 9 · 2019: 16 · 2018: 17 · 2017: 13 · 2016: 17 · 2015: 16 · 2014: 17 · 2013: 17 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- NBS1, MRE11, RAD50, Mre11-Rad50-Nbs1 complex, DNA double-strand break repair, DNA unwinding, endonuclease cleavage, ATP binding, protein-DNA complex, Nijmegen breakage syndrome, meiotic recombination, telomere maintenance
- MeSH terms
- Ku Autoantigen, Adenosine Triphosphate, DNA, DNA Repair, DNA Helicases, DNA-Binding Proteins, DNA, Single-Stranded, Endodeoxyribonucleases, Endonucleases, Exodeoxyribonucleases, Fungal Proteins, HeLa Cells, Humans, Nuclear Proteins, Recombinant Fusion Proteins, Time Factors, Gene Library, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, Antigens, Nuclear
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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