Fission yeast F-box protein Pof3 is required for genome integrity and telomere function.
The Skp1-Cullin-1/Cdc53-F-box protein (SCF) ubiquitin ligase plays an important role in various biological processes. In this enzyme complex, a variety of F-box proteins act as receptors that recruit substrates. We have identified a fission yeast gene encoding a novel F-box protein Pof3, which contains, in addition to the F-box, a tetratricopeptide repeat motif in its N terminus and a leucine-rich-repeat motif in the C terminus, two ubiquitous protein-protein interaction domains. Pof3 forms a complex with Skp1 and Pcu1 (fission yeast cullin-1), suggesting that Pof3 functions as an adaptor for specific substrates. In the absence of Pof3, cells exhibit a number of phenotypes reminiscent of genome integrity defects. These include G2 cell cycle delay, hypersensitivity to UV, appearance of lagging chromosomes, and a high rate of chromosome loss. pof3 deletion strains are viable because the DNA damage checkpoint is continuously activated in the mutant, and this leads to G2 cell cycle delay, thereby preventing the mutant from committing lethal mitosis. Pof3 localizes to the nucleus during the cell cycle. Molecular analysis reveals that in this mutant the telomere is substantially shortened and furthermore transcriptional silencing at the telomere is alleviated. The results highlight a role of the SCF(Pof3) ubiquitin ligase in genome integrity via maintaining chromatin structures.
Katayama
Satoshi
S
Laboratory of Cell Regulation, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.
Kitamura
Kenji
K
Lehmann
Anna
A
Nikaido
Osamu
O
Toda
Takashi
T
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D015825:Chromosomes, Fungal; D016384:Consensus Sequence; D004249:DNA Damage; D044783:F-Box Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D016681:Genome, Fungal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010453:Peptide Synthases / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D016615:Telomere / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects
D018797:Cell Cycle Proteins; D044783:F-Box Proteins; C514993:Pof3 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D044843:SKP Cullin F-Box Protein Ligases; D010453:Peptide Synthases