spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 22 Jun 2004
doi: 10.1242/jcs.01204

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.01204v1
117/16/3489    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Latif, C.
Right arrow Articles by O'Connell, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Latif, C.
Right arrow Articles by O'Connell, M. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

DNA damage checkpoint maintenance through sustained Chk1 activity


Christine Latif, Nicole R. den Elzen, and Matthew J. O'Connell*
* Author for correspondence (e-mail: matthew.oconnell{at}mssm.edu)

The G2 DNA damage checkpoint prevents mitotic entry in the presence of DNA damage. This requires the activation of the phosphoinositide-3-kinase-related protein kinases ATR and ATM in human cells and the ATR homologue Rad3 in the fission yeast Schizosaccharomyces pombe. Rad3 activates the effector protein kinase Chk1 by phosphorylation. However, in fission yeast, inactivation of Rad3 following checkpoint activation has no impact on checkpoint duration. This demonstrates that Rad3 is not required for checkpoint maintenance and that the processes of checkpoint initiation and maintenance are distinct. Chk1 is required for checkpoint initiation but its role in checkpoint maintenance has not been investigated. We show here that Chk1 kinase activity is rapidly induced following irradiation and is maintained for the duration of a checkpoint arrest. On entry to mitosis, there is a transient decrease in Chk1 activity and phosphorylation, but Chk1 activity remains higher than that observed in unirradiated cells. We have generated temperature-sensitive alleles of chk1, which phenocopy chk1 deletion at the non-permissive temperature. Using these alleles, we have shown that inactivation of Chk1 during a checkpoint arrest leads to premature checkpoint termination, resulting in catastrophic mitoses that are a hallmark of checkpoint failure. Therefore, unlike Rad3, Chk1 is an important determinant of both checkpoint initiation and maintenance.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
A. Kosoy and M. J. O'Connell
Regulation of Chk1 by Its C-terminal Domain
Mol. Biol. Cell, November 1, 2008; 19(11): 4546 - 4553.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
C. Rostek, E. L. Turner, M. Robbins, S. Rightnar, W. Xiao, A. Obenaus, and T. A. A. Harkness
Involvement of homologous recombination repair after proton-induced DNA damage
Mutagenesis, March 1, 2008; 23(2): 119 - 129.
[Abstract] [Full Text] [PDF]

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 page
 GeneticsHome page
K. M. Lee, S. Nizza, T. Hayes, K. L. Bass, A. Irmisch, J. M. Murray, and M. J. O'Connell
Brc1-Mediated Rescue of Smc5/6 Deficiency: Requirement for Multiple Nucleases and a Novel Rad18 Function
Genetics, April 1, 2007; 175(4): 1585 - 1595.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
T. M. Calonge and M. J. O'Connell
Antagonism of Chk1 Signaling in the G2 DNA Damage Checkpoint by Dominant Alleles of Cdr1
Genetics, September 1, 2006; 174(1): 113 - 123.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
V. O'Brien and R. Brown
Signalling cell cycle arrest and cell death through the MMR System
Carcinogenesis, April 1, 2006; 27(4): 682 - 692.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. J. O'Connell and K. A. Cimprich
G2 damage checkpoints: what is the turn-on?
J. Cell Sci., January 1, 2005; 118(1): 1 - 6.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2004