help button home button Genetics PLANT CELL
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published as Genetics Published Articles Ahead of Print on July 18, 2006.

Genetics, Vol. 174, 155-165, September 2006, Copyright © 2006
doi:10.1534/genetics.106.060053

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
genetics.106.060053v1
174/1/155    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nitani, N.
Right arrow Articles by Nakagawa, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nitani, N.
Right arrow Articles by Nakagawa, T.

Regulation of DNA Replication Machinery by Mrc1 in Fission Yeast

Naoki Nitani*, Ken-ichi Nakamura*,{dagger}, Chie Nakagawa*, Hisao Masukata*,{dagger} and Takuro Nakagawa*,1

* Department of Biological Science, Graduate School of Science and {dagger} Graduate School of Frontier Biosciences, Osaka University, Osaka 560-0043, Japan

1 Corresponding author: Department of Biological Science, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
E-mail: takuro4{at}bio.sci.osaka-u.ac.jp

Faithful replication of chromosomes is crucial to genome integrity. In yeast, the ORC binds replication origins throughout the cell cycle. However, Cdc45 binds these before S-phase, and, during replication, it moves along the DNA with MCM helicase. When replication progression is inhibited, checkpoint regulation is believed to stabilize the replication fork; the detailed mechanism, however, remains unclear. To examine the relationship between replication initiation and elongation defects and the response to replication elongation block, we used fission yeast mutants of Orc1 and Cdc45—orp1-4 and sna41-928, respectively—at their respective semipermissive temperatures with regard to BrdU incorporation. Both orp1 and sna41 cells exhibited HU hypersensitivity in the absence of Chk1, a DNA damage checkpoint kinase, and were defective in full activation of Cds1, a replication checkpoint kinase, indicating that normal replication is required for Cds1 activation. Mrc1 is required to activate Cds1 and prevent the replication machinery from uncoupling from DNA synthesis. We observed that, while either the orp1 or the sna41 mutation partially suppressed HU sensitivity of cds1 cells, sna41 specifically suppressed that of mrc1 cells. Interestingly, sna41 alleviated the defect in recovery from HU arrest without increasing Cds1 activity. In addition to sna41, specific mutations of MCM suppressed the HU sensitivity of mrc1 cells. Thus, during elongation, Mrc1 may negatively regulate Cdc45 and MCM helicase to render stalled forks capable of resuming replication.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
G. H. Enders
Expanded Roles for Chk1 in Genome Maintenance
J. Biol. Chem., June 27, 2008; 283(26): 17749 - 17752.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the Genetics Society of America.