help button home button Genetics AJP: Lung
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published as Genetics Published Articles Ahead of Print on July 2, 2006.

Genetics, Vol. 174, 113-123, September 2006, Copyright © 2006
doi:10.1534/genetics.106.060970

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow All Versions of this Article:
genetics.106.060970v1
174/1/113    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 Calonge, T. M.
Right arrow Articles by O'Connell, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Calonge, T. M.
Right arrow Articles by O'Connell, M. J.

Antagonism of Chk1 Signaling in the G2 DNA Damage Checkpoint by Dominant Alleles of Cdr1

Teresa M. Calonge and Matthew J. O'Connell1

Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York 10029

1 Corresponding author: Mount Sinai School of Medicine, 1425 Madison Ave., Room 15-70, New York, New York 10029.
E-mail: matthew.oconnell{at}mssm.edu

Activation of the Chk1 protein kinase by DNA damage enforces a checkpoint that maintains Cdc2 in its inactive, tyrosine-15 (Y15) phosphorylated state. Chk1 downregulates the Cdc25 phosphatases and concomitantly upregulates the Wee1 kinases that control the phosphorylation of Cdc2. Overproduction of Chk1 causes G2 arrest/delay independently of DNA damage and upstream checkpoint genes. We utilized this to screen fission yeast for mutations that alter sensitivity to Chk1 signaling. We describe three dominant-negative alleles of cdr1, which render cells supersensitive to Chk1 levels, and suppress the checkpoint defects of chk1{Delta} cells. Cdr1 encodes a protein kinase previously identified as a negative regulator of Wee1 activity in response to limited nutrition, but Cdr1 has not previously been linked to checkpoint signaling. Overproduction of Cdr1 promotes checkpoint defects and exacerbates the defective response to DNA damage of cells lacking Chk1. We conclude that regulation of Wee1 by Cdr1 and possibly by related kinases is an important antagonist of Chk1 signaling and represents a novel negative regulation of cell cycle arrest promoted by this checkpoint.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. Kosoy, T. M. Calonge, E. A. Outwin, and M. J. O'Connell
Fission Yeast Rnf4 Homologs Are Required for DNA Repair
J. Biol. Chem., July 13, 2007; 282(28): 20388 - 20394.
[Abstract] [Full Text] [PDF]


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