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Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex

Academic Article
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Overview

authors

  • McDonald, W. H.
  • Pavlova, Y.
  • Yates III, John
  • Boddy, Michael

publication date

  • November 2003

journal

  • Journal of Biological Chemistry  Journal

abstract

  • The structural maintenance of chromosomes (SMC) family of proteins play essential roles in genomic stability. SMC heterodimers are required for sister-chromatid cohesion (Cohesin: Smc1 & Smc3), chromatin condensation (Condensin: Smc2 & Smc4), and DNA repair (Smc5 & Smc6). The SMC heterodimers do not function alone and must associate with essential non-SMC subunits. To gain further insight into the essential and DNA repair roles of the Smc5-6 complex, we have purified fission yeast Smc5 and identified by mass spectrometry the co-precipitating proteins, Nse1 and Nse2. We show that both Nse1 and Nse2 interact with Smc5 in vivo, as part of the Smc5-6 complex. Nse1 and Nse2 are essential proteins and conserved from yeast to man. Loss of Nse1 and Nse2 function leads to strikingly similar terminal phenotypes to those observed for Smc5-6 inactivation. In addition, cells expressing hypomorphic alleles of Nse1 and Nse2 are, like Smc5-6 mutants, hypersensitive to DNA damage. Epistasis analysis suggests that like Smc5-6, Nse1, and Nse2 function together with Rhp51 in the homologous recombination repair of DNA double strand breaks. The results of this study strongly suggest that Nse1 and Nse2 are novel non-SMC subunits of the fission yeast Smc5-6 DNA repair complex.

subject areas

  • Alleles
  • Amino Acid Sequence
  • Cell Cycle Proteins
  • Cell Nucleus
  • Chromatin
  • Chromatography, Gel
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • Dimerization
  • Dose-Response Relationship, Radiation
  • Gene Deletion
  • Mass Spectrometry
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins
  • Peptides
  • Phenotype
  • Rad51 Recombinase
  • Recombination, Genetic
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins
  • Sequence Homology, Amino Acid
  • Temperature
  • Ultraviolet Rays
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M308828200

PubMed ID

  • 12966087
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Additional Document Info

start page

  • 45460

end page

  • 45467

volume

  • 278

issue

  • 46

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