Abstract
Stabilization and processing of stalled replication forks is critical for cell survival and genomic integrity. We characterize a novel DNA repair heterodimer of Nse5 and Nse6, which are nonessential nuclear proteins critical for chromosome segregation in fission yeast. The Nse5/6 dimer facilitates DNA repair as part of the Smc5-Smc6 holocomplex (Smc5/6), the basic architecture of which we define. Nse5-Nse6 [corrected] (Nse5 and Nse6) [corrected] mutants display a high level of spontaneous DNA damage and mitotic catastrophe in the absence of the master checkpoint regulator Rad3 (hATR). Nse5/6 mutants are required for the response to genotoxic agents that block the progression of replication forks, acting in a pathway that allows the tolerance of irreparable UV lesions. Interestingly, the UV sensitivity of Nse5/6 [corrected] is suppressed by concomitant deletion of the homologous recombination repair factor, Rhp51 (Rad51). Further, the viability of Nse5/6 mutants depends on Mus81 and Rqh1, factors that resolve or prevent the formation of Holliday junctions. Consistently, the UV sensitivity of cells lacking Nse5/6 can be partially suppressed by overexpressing the bacterial resolvase RusA. We propose a role for Nse5/6 mutants in suppressing recombination that results in Holliday junction formation or in Holliday junction resolution.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism*
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DNA Helicases / genetics
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DNA Helicases / metabolism
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DNA Repair / physiology*
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DNA Replication / physiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Dimerization
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Endonucleases / genetics
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Endonucleases / metabolism
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / metabolism
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Genome, Fungal / genetics
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Genomic Instability
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Holliday Junction Resolvases / genetics
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Holliday Junction Resolvases / metabolism
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Multiprotein Complexes
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Mutation
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Recombination, Genetic
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Schizosaccharomyces / genetics
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Schizosaccharomyces / radiation effects
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Schizosaccharomyces pombe Proteins / genetics
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Schizosaccharomyces pombe Proteins / metabolism*
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Ultraviolet Rays
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Escherichia coli Proteins
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MUS81 protein, S pombe
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Multiprotein Complexes
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Nse5 protein, S pombe
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Nse6 protein, S pombe
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Nuclear Proteins
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Recombinant Proteins
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Schizosaccharomyces pombe Proteins
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Smc5 protein, S pombe
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smc6 protein, S pombe
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Endonucleases
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Holliday Junction Resolvases
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RusA protein, E coli
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DNA Helicases
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Rqh1 protein, S pombe