The F-box protein Dia2 regulates DNA replication.

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.

journal_name

Mol Biol Cell

authors

Koepp DM,Kile AC,Swaminathan S,Rodriguez-Rivera V

doi

10.1091/mbc.e05-09-0884

keywords:

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

1540-8

issue

4

eissn

1059-1524

issn

1939-4586

pii

E05-09-0884

journal_volume

17

pub_type

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