title: The F-box protein Dia2 regulates DNA replication.
abstract: Ubiquitin-mediated proteolysis plays a key role in many pathways inside the cell and is particularly important in regulating cell cycle transitions. SCF (Skp1/Cul1/F-box protein) complexes are modular ubiquitin ligases whose specificity is determined by a substrate-binding F-box protein. Dia2 is a Saccharomyces cerevisiae F-box protein previously described to play a role in invasive growth and pheromone response pathways. We find that deletion of DIA2 renders cells cold-sensitive and subject to defects in cell cycle progression, including premature S-phase entry. Consistent with a role in regulating DNA replication, the Dia2 protein binds replication origins. Furthermore, the dia2 mutant accumulates DNA damage in both S and G2/M phases of the cell cycle. These defects are likely a result of the absence of SCF(Dia2) activity, as a Dia2 DeltaF-box mutant shows similar phenotypes. Interestingly, prolonging G1-phase in dia2 cells prevents the accumulation of DNA damage in S-phase. We propose that Dia2 is an origin-binding protein that plays a role in regulating DNA replication.
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA. koepp015@umn.edu
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Koepp
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Kile
authors.forename: Swarna
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Veronica
authors.initials: V
authors.lastname: Rodriguez-Rivera
mesh_terms: D004249:DNA Damage / Q000235:genetics; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D009154:Mutation; D018741:Replication Origin / Q000235:genetics*; D016196:S Phase / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; C495983:Dia2 protein, S cerevisiae; D044783:F-Box Proteins; D029701:Saccharomyces cerevisiae Proteins; D044843:SKP Cullin F-Box Protein Ligases