The Nse5-Nse6 dimer mediates DNA repair roles of the Smc5-Smc6 complex.
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.
The Scripps Research Institute, Rm. MB107, 10550 North Torrey Pines Rd., Molecular Biology, MB-3, La Jolla, CA 92037, USA.
Stephanie
S
Pebernard
James
J
Wohlschlegel
W Hayes
WH
McDonald
John R
JR
Yates
Michael N
MN
Boddy
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal / Q000235:genetics; D042822:Genomic Instability; D045565:Holliday Junction Resolvases / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000235:genetics / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C495865:MUS81 protein, S pombe; D046912:Multiprotein Complexes; C577314:Nse5 protein, S pombe; C577313:Nse6 protein, S pombe; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D029702:Schizosaccharomyces pombe Proteins; C486628:Smc5 protein, S pombe; C486630:smc6 protein, S pombe; D004720:Endonucleases; D045565:Holliday Junction Resolvases; C112057:RusA protein, E coli; D004265:DNA Helicases; C106462:Rqh1 protein, S pombe