Journal
CURRENT BIOLOGY
Volume 21, Issue 24, Pages 2055-2063Publisher
CELL PRESS
DOI: 10.1016/j.cub.2011.11.038
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Grants-in-Aid for Scientific Research [22019039, 22221009, 23710230, 20227004, 20370005, 22125001] Funding Source: KAKEN
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Background: Chromosomal DNA replication in eukaryotes initiates from multiple origins of replication, and because of this multiplicity, activation of replication origins is likely to be highly coordinated; origins fire at characteristic times, with some origins firing on average earlier (early-firing origins) and others later (late-firing origins) in the S phase of the budding yeast cell cycle. However, the molecular basis for such temporal regulation is poorly understood. Results: We show that origin association of the low-abundance replication proteins SId3, SId7, and Cdc45 is the key to determining the temporal order of origin firing. These proteins form a complex and associate with the early-firing origins in G1 phase in a manner that depends on Dbf4-dependent kinase (DDK), which is essential for the initiation of DNA replication. An increased dosage of 5Id3, SId7, and Cdc45 allows the late-firing origins to fire earlier in S phase. Additionally, an increased dosage of DDK also allows the late-firing origins to fire earlier. Conclusions: The DDK-dependent limited association between origins and SId3-SId7-Cdc45 is a key step for determining the timing of origin firing.
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