Cited by 551DNA Repair MechanismsDNA and Nucleic Acid ChemistryCRISPR and Genetic Engineering

Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex

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Paull, T. T., Gellert, M.·1999·Genes & Development

Abstract

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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Crossref · 10.1101/gad.13.10.1276

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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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  1. Petes, T.D., R.E. Malone, and L.S. Symington. 1991. Recombi- nation in yeast. In The molecular and cellular biology of the yeast Saccharomyces (eds. J.R. Broach, E.W. Jones, and J.R. Pringle), pp. 407-521. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

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Authors
Paull, T. T., & Gellert, M.
Affiliations
National Institutes of Health (US)
Venue
Genes & Development
Published
1999-05-15
Volume
13
Issue
10
Pages
1276-1288
ISSN
0890-9369 (ISSN-L)
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
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

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