title: The Arabidopsis COP9 signalosome is essential for G2 phase progression and genomic stability.
abstract: The COP9 signalosome (CSN) is required for the full activity of cullin-RING E3 ubiquitin ligases (CRLs) in eukaryotes. CSN exerts its function on CRLs by removing the ubiquitin-related NEDD8 conjugate from the cullin subunit of CRLs. CSN seems, thereby, to control CRL disassembly or CRL subunit stability. In Arabidopsis thaliana, loss of CSN function leads to constitutive photomorphogenic (cop) seedling development and a post-germination growth arrest. The underlying molecular cause of this growth arrest is currently unknown. Here, we show that Arabidopsis csn mutants are delayed in G2 phase progression. This cell cycle arrest correlates with the induction of the DNA damage response pathway and is suggestive of the activation of a DNA damage checkpoint. In support of this hypothesis, we detected gene conversion events in csn mutants that are indicative of DNA double-strand breaks. DNA damage is also apparent in mutants of the NEDD8 conjugation pathway and in mutants of the E3 ligase subunits CULLIN4, COP1 and DET1, which share phenotypes with csn mutants. In summary, our data suggest that Arabidopsis csn mutants undergo DNA damage, which might be the cause of the delay in G2 cell cycle progression.
authors.affiliation: Tübingen University, Center for Plant Molecular Biology, Department of Developmental Genetics, Auf der Morgenstelle 3-5, 72076 Tübingen, Germany.
authors.forename: Esther M N
authors.initials: EM
authors.lastname: Dohmann
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Levesque
authors.forename: Lieven
authors.initials: L
authors.lastname: De Veylder
authors.forename: Ilka
authors.initials: I
authors.lastname: Reichardt
authors.forename: Gerd
authors.initials: G
authors.lastname: Jürgens
authors.forename: Markus
authors.initials: M
authors.lastname: Schmid
authors.forename: Claus
authors.initials: C
authors.lastname: Schwechheimer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D000075686:COP9 Signalosome Complex; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005434:Flow Cytometry; D016195:G2 Phase / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018506:Gene Expression Regulation, Plant; D042822:Genomic Instability; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D018517:Plant Roots / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D036226:Seedlings / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: C522744:ATM2 protein, Arabidopsis; D018528:ATP-Binding Cassette Transporters; D029681:Arabidopsis Proteins; C497728:COP9 signalosome subunit 5, Arabidopsis; C514806:CULLIN4 protein, Arabidopsis; D044842:Cullin Proteins; C462528:CycB1 protein, Arabidopsis; D019926:Cyclin B; C088435:DET1 protein, Arabidopsis; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C513170:RUB1 protein, Arabidopsis; D014452:Ubiquitins; C471983:AT2G32950 protein, Arabidopsis; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C514674:WEE1 protein, Arabidopsis; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex