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MBC in Press, published online ahead of print January 18, 2006
Mol. Biol. Cell 10.1091/mbc.E05-09-0884

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Submitted on September 21, 2005
Revised on December 27, 2005
Accepted on January 9, 2006

The F-Box Protein Dia2 Regulates DNA Replication

Deanna M. Koepp, Andrew C. Kile,* Swarna Swaminathan,* and Veronica Rodriguez-Rivera

Department of Genetics, Cell Biology, and Development, University of Minnesota-Twin Cities, Minneapolis, MN 55455

Monitoring Editor: William Tansey

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 S. 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 SCFDia2 activity, as a Dia2 {Delta}F-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.

*These authors contributed equally to this work.

Address correspondence to: Deanna M. Koepp (koepp015{at}umn.edu)




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