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


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 7 December 2004
doi: 10.1242/jcs.01599

Journal of Cell Science 118, 101-112 (2005)
Published by The Company of Biologists 2005
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
jcs.01599v1
118/1/101    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 Related articles in JCS
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 Coverley, D.
Right arrow Articles by Ainscough, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coverley, D.
Right arrow Articles by Ainscough, J.

Research Article

Ciz1 promotes mammalian DNA replication

Dawn Coverley1,2,*, Jackie Marr2 and Justin Ainscough3

1 Department of Biology (Area 9), University of York, York, YO10 5YW, UK
2 Hutchison/MRC Research Centre, MRC Cancer Cell Unit, Hills Road, Cambridge, CB2 2XZ, UK
3 Heart Research Centre and CRISTAL, Leeds University, Leeds, LS2 9JT, UK

* Author for correspondence (e-mail: dc17{at}york.ac.uk)

Accepted 19 October 2004

Using a cell-free system that reconstitutes initiation of mammalian DNA replication, we identified a cyclin A-responsive protein, p21Cip1-interacting zinc finger protein 1 (Ciz1). In cell-free experiments, Ciz1 protein increases the number of nuclei that initiate DNA replication, and in intact cells GFP-tagged Ciz1 stimulates DNA synthesis, in both a wild-type and a p21Cip1 null background. Furthermore, mutation of a putative cyclin-dependent kinase phosphorylation site at threonines 191/2 alters Ciz1 activity in vitro, indicating that this site plays a role in regulating Ciz1. Consistent with a role in DNA replication, endogenous Ciz1 is present in nuclear foci that co-localize with PCNA during S phase, and targeted depletion of Ciz1 transcripts restrains cell proliferation by inhibiting entry to S phase. Ciz1-depleted cells accumulate with chromatin bound Mcm3 and PCNA but fail to synthesize DNA efficiently. These cell-based and cell-free experiments suggest that Ciz1 functions to promote DNA replication after replication complex formation. Finally, alternatively spliced forms of Ciz1 occur in embryonic cells from mouse and man, raising the possibility that Ciz1 splicing contributes to the regulation of DNA replication during development.

Key words: DNA replication, Cell cycle, Ciz1, Alternative splicing


Related articles in JCS:

Ciz1: a new player in DNA replication

JCS 2005 118: 106. [Full Text]  



This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
J. F.-X. Ainscough, F. A. Rahman, H. Sercombe, A. Sedo, B. Gerlach, and D. Coverley
C-terminal domains deliver the DNA replication factor Ciz1 to the nuclear matrix
J. Cell Sci., January 1, 2007; 120(1): 115 - 124.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. den Hollander, S. K. Rayala, D. Coverley, and R. Kumar
Ciz1, a Novel DNA-Binding Coactivator of the Estrogen Receptor {alpha}, Confers Hypersensitivity to Estrogen Action.
Cancer Res., November 15, 2006; 66(22): 11021 - 11029.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. den Hollander and R. Kumar
Dynein Light Chain 1 Contributes to Cell Cycle Progression by Increasing Cyclin-Dependent Kinase 2 Activity in Estrogen-Stimulated Cells
Cancer Res., June 1, 2006; 66(11): 5941 - 5949.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005