| Title: | The F-box protein Dia2 regulates DNA replication |
| Author(s): | Koepp DM; Kile AC; Swaminathan S; Rodriguez-Rivera V; |
| Address: | "Department of Genetics, Cell Biology, and Development, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA. koepp015@umn.edu" |
| ISSN/ISBN: | 1059-1524 (Print) 1059-1524 (Linking) |
| 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" |
| Keywords: | "DNA Damage/genetics *DNA Replication DNA, Fungal/metabolism F-Box Proteins/genetics/*metabolism Gene Deletion Mutation Replication Origin/*genetics S Phase/genetics SKP Cullin F-Box Protein Ligases/metabolism Saccharomyces cerevisiae/*genetics Saccharomyc;" |
| Notes: | "MedlineKoepp, Deanna M Kile, Andrew C Swaminathan, Swarna Rodriguez-Rivera, Veronica eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2006/01/20 Mol Biol Cell. 2006 Apr; 17(4):1540-8. doi: 10.1091/mbc.e05-09-0884. Epub 2006 Jan 18" |
