Novel Essential DNA Repair Proteins Nse1 and Nse2 Are Subunits of the Fission Yeast Smc5-Smc6 Complex
Copyright policy )Novel Essential DNA Repair Proteins Nse1 and Nse2 Are Subunits of the Fission Yeast Smc5-Smc6 Complex
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.
- Scripps Research Institute United States
Cell Nucleus, Recombination, Genetic, DNA Repair, Molecular Sequence Data, Nuclear Proteins, Cell Cycle Proteins, Dose-Response Relationship, Radiation, Chromatin, Mass Spectrometry, DNA-Binding Proteins, Phenotype, Mutation, Chromatography, Gel, Amino Acid Sequence, Rad51 Recombinase, Peptides, Dimerization, Alleles, Gene Deletion, DNA Damage
Cell Nucleus, Recombination, Genetic, DNA Repair, Molecular Sequence Data, Nuclear Proteins, Cell Cycle Proteins, Dose-Response Relationship, Radiation, Chromatin, Mass Spectrometry, DNA-Binding Proteins, Phenotype, Mutation, Chromatography, Gel, Amino Acid Sequence, Rad51 Recombinase, Peptides, Dimerization, Alleles, Gene Deletion, DNA Damage
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