| Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
mrc1Δ and rif1Δ can bypass the requirement of Hsk1 kinase. mrc1-3A, specifically defective in checkpoint, and mrc1ΔHBS (Δ782-879), proficient in checkpoint, can independently rescue hsk1ts, albeit less efficiently, and combination of mrc1-3A and mrc1ΔHBS rescues hsk1ts almost as efficiently as mrc1Δ, confirming that mrc1Δ can bypass Hsk1 in both checkpoint-dependent and -independent manners. Initiation of DNA replication is enhanced at early origins in ΔHBS. C-terminus (781-1019) of Mrc1 containing HBS can interact with the N-terminus and inhibits the mrc1ΔHBS-mediated bypass of hsk1ts. Intramolecular interaction between C-terminus and N-terminus renders Mrc1 in an inhibitory conformation, and phosphorylation through HBS causes dissociation of the N-terminal segment from the C-terminus, transforming Mrc1 into a permissive conformation that can rescue hsk1ts. We found a consensus sequence among Rif1-binding regions which is essential for Rif1 to regulate initiation.
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