Analysis of Hsk1 function in genome dynamics regulation by using new Hsk1-bypass mutants
| Project/Area Number |
24570205
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Molecular biology
|
|---|
| Research Institution | Tokyo Metropolitan Institute of Medical Science |
|---|
Principal Investigator |
MATSUMOTO Seiji 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主任研究員 (40190532)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| 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)
|
|---|
| Keywords | DNA複製 / 複製タイミング / CDC7 / hsk1 / mrc1 / rif1 / 分裂酵母 / 複製起点 / Cdc7 / 複製開始点 / Hsk1 / Rif1 / Mrc1 |
|---|
| 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.
|
Report
(4 results)
Research Products
(9 results)
