QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E05-09-0884v1 17/4/1540    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koepp, D. M. Articles by Rodriguez-Rivera, V. Search for Related Content PubMed PubMed Citation Articles by Koepp, D. M. Articles by Rodriguez-Rivera, V.

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).

This article has been cited by other articles:

				S. Swaminathan, A. C. Kile, E. M. MacDonald, and D. M. Koepp Yra1 Is Required for S Phase Entry and Affects Dia2 Binding to Replication Origins Mol. Cell. Biol., July 1, 2007; 27(13): 4674 - 4684. [Abstract] [Full Text] [PDF]

				K. W. Y. Yuen, C. D. Warren, O. Chen, T. Kwok, P. Hieter, and F. A. Spencer Systematic genome instability screens in yeast and their potential relevance to cancer PNAS, March 6, 2007; 104(10): 3925 - 3930. [Abstract] [Full Text] [PDF]

				D. Blake, B. Luke, P. Kanellis, P. Jorgensen, T. Goh, S. Penfold, B.-J. Breitkreutz, D. Durocher, M. Peter, and M. Tyers The F-Box Protein Dia2 Overcomes Replication Impedance to Promote Genome Stability in Saccharomyces cerevisiae Genetics, December 1, 2006; 174(4): 1709 - 1727. [Abstract] [Full Text] [PDF]