The F-Box Protein Dia2 Regulates DNA Replication

• Published in: Molecular biology of the cell Vol. 17; no. 4; pp. 1540 - 1548
• Main Authors: Koepp, Deanna M., Kile, Andrew C., Swaminathan, Swarna, Rodriguez-Rivera, Veronica
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 01.04.2006
• Subjects: 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; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; SKP Cullin F-Box Protein Ligases - metabolism
• ISSN: 1059-1524; 1939-4586; 1059-1524
• DOI: 10.1091/mbc.e05-09-0884

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 ΔF-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.