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| Genetics Dec (2006); 174(4):1709-27 | |
| The F-Box Protein Dia2 Overcomes Replication Impedance to Promote Genome Stability in Saccharomyces cerevisiae- | |
| Blake D, Luke B, Kanellis P, Jorgensen P, Goh T, Penfold S, Breitkreutz BJ, Durocher D, Peter M, Tyers M | |
| Institute of Biochemistry, 8093 Zurich, Switzerland- | |
| Abstract: The maintenance of DNA replication fork stability under conditions of DNA damage and at natural replication pause sites is essential for genome stability- Here, we describe a novel role for the F-box protein Dia2 in promoting genome stability in the budding yeast Saccharomyces cerevisiae- Like most other F-box proteins, Dia2 forms a Skp1-Cdc53-Cullin-F-box -SCF- E3 ubiquitin-ligase complex- Systematic analysis of genetic interactions between dia2Delta and approximately 4400 viable gene deletion mutants revealed synthetic lethal-synthetic sick interactions with a broad spectrum of DNA replication, recombination, checkpoint, and chromatin-remodeling pathways- dia2Delta strains exhibit constitutive activation of the checkpoint kinase Rad53 and elevated counts of endogenous DNA repair foci and are unable to overcome MMS-induced replicative stress- Notably, dia2Delta strains display a high rate of gross chromosomal rearrangements -GCRs- that involve the rDNA locus and an increase in extrachromosomal rDNA circle -ERC- formation, consistent with an observed enrichment of Dia2 in the nucleolus- These results suggest that Dia2 is essential for stable passage of replication forks through regions of damaged DNA and natural fragile regions, particularly the replication fork barrier -RFB- of rDNA repeat loci- We propose that the SCF-Dia2- ubiquitin ligase serves to modify or degrade protein substrates that would otherwise impede the replication fork in problematic regions of the genome- | |
| [PUBMED: 16751663] |   |
| Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |