PMID:16421250

Citation	Koepp, DM, Kile, AC, Swaminathan, S and Rodriguez-Rivera, V (2006) The F-box protein Dia2 regulates DNA replication. Mol. Biol. Cell 17:1540-8
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.
Links	PubMed PMC1415285 Online version:10.1091/mbc.E05-09-0884
Keywords	DNA Damage/genetics; DNA Replication; DNA, Fungal/metabolism; F-Box Proteins/genetics; F-Box Proteins/metabolism; Gene Deletion; Mutation; Replication Origin/genetics; S Phase/genetics; SKP Cullin F-Box Protein Ligases/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism
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