2017年4月1日
Checkpoint-Independent Regulation of Origin Firing by Mrc1 through Interaction with Hsk1 Kinase.
Molecular and cellular biology
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- 巻
- 37
- 号
- 7
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1128/MCB.00355-16
- 出版者・発行元
- AMER SOC MICROBIOLOGY
Mrc1 is a conserved checkpoint mediator protein that transduces the replication stress signal to the downstream effector kinase. The loss of mrc1 checkpoint activity results in the aberrant activation of late/dormant origins in the presence of hydroxyurea. Mrc1 was also suggested to regulate orders of early origin firing in a checkpoint-independent manner, but its mechanism was unknown. Here we identify HBS (Hsk1 bypass segment) on Mrc1. An ΔHBS mutant does not activate late/dormant origin firing in the presence of hydroxyurea but causes the precocious and enhanced activation of weak early-firing origins during normal S-phase progression and bypasses the requirement for Hsk1 for growth. This may be caused by the disruption of intramolecular binding between HBS and NTHBS (N-terminal target of HBS). Hsk1 binds to Mrc1 through HBS and phosphorylates a segment adjacent to NTHBS, disrupting the intramolecular interaction. We propose that Mrc1 exerts a "brake" on initiation (through intramolecular interactions) and that this brake can be released (upon the loss of intramolecular interactions) by either the Hsk1-mediated phosphorylation of Mrc1 or the deletion of HBS (or a phosphomimic mutation of putative Hsk1 target serine/threonine), which can bypass the function of Hsk1 for growth. The brake mechanism may explain the checkpoint-independent regulation of early origin firing in fission yeast.
- リンク情報
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- DOI
- https://doi.org/10.1128/MCB.00355-16
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/28069740
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359423
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000397578200002&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-85015421169&partnerID=MN8TOARS
- ID情報
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- DOI : 10.1128/MCB.00355-16
- ISSN : 0270-7306
- eISSN : 1098-5549
- ORCIDのPut Code : 101136787
- PubMed ID : 28069740
- PubMed Central 記事ID : PMC5359423
- SCOPUS ID : 85015421169
- Web of Science ID : WOS:000397578200002