title: Qri2/Nse4, a component of the essential Smc5/6 DNA repair complex.
abstract: We demonstrate a role for Qri2 in the essential DNA repair function of the Smc5/6 complex in Saccharomyces cerevisiae. We generated temperature-sensitive (ts) mutants in QRI2 and characterized their properties. The mutants arrest after S phase and prior to mitosis. Furthermore, the arrest is dependant on the Rad24 checkpoint, and is also accompanied by phosphorylation of the Rad53 checkpoint effector kinase. The mutants also display genome instability and are sensitive to agents that damage DNA. Two-hybrid screens reveal a physical interaction between Qri2 and proteins that are non-Smc elements of the Smc5/6 DNA repair complex, which is why we propose the name NSE4 for the open reading frame previously known as QRI2. A key role for Nse4 in Smc5/6 function is likely, as overexpressing known subunits of the Smc5/6 complex suppresses nse4(ts) cell cycle arrest. The nse4(ts) growth arrest is non-lethal and unlike the catastrophic nuclear fragmentation phenotype of smc6(ts) mutants, the nucleus remains intact; replicative intermediates and sheared DNA are not detected. This could imply a role for Nse4 in maintenance of higher order chromosome structure.
authors.affiliation: Department of Life Sciences, King's College London, London SE1 9NN, UK.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liao
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Millson
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mollapour
authors.forename: Chrisostomos
authors.initials: C
authors.lastname: Prodromou
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Pearl
authors.forename: Peter W
authors.initials: PW
authors.lastname: Piper
authors.forename: Barry
authors.initials: B
authors.lastname: Panaretou
mesh_terms: D000595:Amino Acid Sequence; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D064447:Checkpoint Kinase 2; D022004:Chromosome Structures / Q000502:physiology; D004260:DNA Repair; D005800:Genes, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D020798:Two-Hybrid System Techniques
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C501992:NSE4 protein, S cerevisiae; C088385:RAD24 protein, S cerevisiae; C486627:SMC5 protein, S cerevisiae; C486631:SMC6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae