The F-box protein Dia2 regulates DNA replication

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

Research output: Contribution to journalArticle

35 Scopus citations

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 SCFDia2 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.

Original languageEnglish (US)
Pages (from-to)1540-1548
Number of pages9
JournalMolecular biology of the cell
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2006

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