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Status |
Public on Aug 26, 2011 |
Title |
Multiple bypass pathways of Hsk1 kinase essential for initiation of DNA replication in fission yeast |
Organism |
Schizosaccharomyces pombe |
Experiment type |
Genome binding/occupancy profiling by genome tiling array
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Summary |
Cdc7/Hsk1 is a conserved kinase required for initiation of DNA replication that potentially regulates timing and locations of replication origin firing. Here, we show that viability of fission yeast hsk1∆ cells can be restored by loss of mrc1, which is required for maintenance of replication fork integrity, by cds1∆, or by a checkpoint-deficient mutant of mrc1. In these mutants, normally inactive origins are activated in the presence of HU and binding of Cdc45 to MCM is stimulated. mrc1∆ bypasses hsk1∆ more efficiently because of its checkpoint-independent inhibitory functions. Unexpectedly, hsk1∆ is viable at 37°C. More DNA is synthesized, and some dormant origins fire in the presence of HU at 37°C. On the other hand, hsk1∆ bypass strains grow poorly at 25°C compared to at higher temperatures. Our results show that Hsk1 functions for DNA replication can be bypassed by different genetic backgrounds as well as under varied physiological conditions, providing additional evidence for plasticity of the replication program in eukaryotes. BrdU incorporation profiles at early S-phase in mrc1∆, cds1∆ and hsk1-89 mutants.
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Overall design |
BrdU-incorporated region at early S-phase vs. Input at Metaphase sample
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Contributor(s) |
Matsumoto S, Hayano M, Kanoh Y, Masai H |
Citation(s) |
22024164 |
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Submission date |
Aug 25, 2011 |
Last update date |
May 27, 2014 |
Contact name |
Yutaka Kanoh |
E-mail(s) |
kanou-yt@igakuken.or.jp
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Organization name |
Tokyo Metropolitan Institute of Medical Science
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Department |
Genome Medicine
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Lab |
Genome Dynamics Projec
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Street address |
2-1-6 Kamikitazawa, Setagaya-ku
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City |
Tokyo |
ZIP/Postal code |
156-8506 |
Country |
Japan |
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Platforms (1) |
GPL7715 |
[Sp20b_M] Affymetrix S. pombe Tiling 1.0FR Array |
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Samples (4)
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Relations |
BioProject |
PRJNA145303 |