PMID:18434413

Citation	Dohmann, EM, Levesque, MP, De Veylder, L, Reichardt, I, Jürgens, G, Schmid, M and Schwechheimer, C (2008) The Arabidopsis COP9 signalosome is essential for G2 phase progression and genomic stability. Development 135:2013-22
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.
Links	PubMed Online version:10.1242/dev.020743
Keywords	ATP-Binding Cassette Transporters/genetics; ATP-Binding Cassette Transporters/metabolism; Arabidopsis Proteins/genetics; Arabidopsis Proteins/metabolism; Cell Cycle/genetics; Cell Cycle/physiology; Cell Division/genetics; Cell Division/physiology; Cullin Proteins/genetics; Cullin Proteins/metabolism; Cyclin B/genetics; Cyclin B/metabolism; DNA Damage; Flow Cytometry; G2 Phase/genetics; G2 Phase/physiology; Gene Expression Regulation, Developmental; Gene Expression Regulation, Plant; Genomic Instability; Immunoblotting; In Situ Nick-End Labeling; Multiprotein Complexes/genetics; Multiprotein Complexes/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Oligonucleotide Array Sequence Analysis; Peptide Hydrolases/genetics; Peptide Hydrolases/metabolism; Plant Roots/genetics; Plant Roots/growth & development; Plant Roots/metabolism; Protein Kinases/genetics; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Seedling/genetics; Seedling/growth & development; Seedling/metabolism; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism; Ubiquitins/genetics; Ubiquitins/metabolism
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