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Vol. 17, Issue 4, 1540-1548, April 2006

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The F-Box Protein Dia2 Regulates DNA Replication

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

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

Abbreviations used: SCF, Skp1-Cdc53-F-box protein; HU, hydroxyurea; WT, wild type; YFP, yellow fluorescent protein.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

^* These authors contributed equally to this work.

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

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