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 14 Mar 2006
doi: 10.1242/jcs.02851

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.02851v1
119/7/1371    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 Saha, T.
Right arrow Articles by DePamphilis, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saha, T.
Right arrow Articles by DePamphilis, M. L.
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

Ubiquitylation, phosphorylation and Orc2 modulate the subcellular location of Orc1 and prevent it from inducing apoptosis


Tapas Saha, Soma Ghosh, Alex Vassilev, and Melvin L. DePamphilis*
* Author for correspondence (e-mail: depamphm{at}mail.nih.gov)

Previous studies have suggested that the activity of the mammalian origin recognition complex (ORC) is regulated by cell-cycle-dependent changes in its Orc1 subunit. Here, we show that Orc1 modifications such as mono-ubiquitylation and hyperphosphorylation that occur normally during S and G2-M phases, respectively, can cause Orc1 to accumulate in the cytoplasm. This would suppress reassembly of pre-replication complexes until mitosis is complete. In the absence of these modifications, transient expression of Orc1 rapidly induced p53-independent apoptosis, and Orc1 accumulated perinuclearly rather than uniformly throughout the nucleus. This behavior mimicked the increased concentration and perinuclear accumulation of endogenous Orc1 in apoptotic cells that arise spontaneously in proliferating cell cultures. Remarkably, expression of Orc1 in the presence of an equivalent amount of Orc2, the only ORC subunit that did not induce apoptosis, prevented induction of apoptosis and restored uniform nuclear localization of Orc1. This would promote assembly of ORC-chromatin sites, such as occurs during the transition from M to G1 phase. These results provide direct evidence in support of the regulatory role proposed for Orc1, and suggest that aberrant DNA replication during mammalian development could result in apoptosis through the appearance of 'unmodified' Orc1.
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
 Eukaryot CellHome page
A. Gupta, P. Mehra, A. Deshmukh, A. Dar, P. Mitra, N. Roy, and S. K. Dhar
Functional Dissection of the Catalytic Carboxyl-Terminal Domain of Origin Recognition Complex Subunit 1 (PfORC1) of the Human Malaria Parasite Plasmodium falciparum
Eukaryot. Cell, September 1, 2009; 8(9): 1341 - 1351.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
N. Sugimoto, K. Yoshida, Y. Tatsumi, T. Yugawa, M. Narisawa-Saito, S. Waga, T. Kiyono, and M. Fujita
Redundant and differential regulation of multiple licensing factors ensures prevention of re-replication in normal human cells
J. Cell Sci., April 15, 2009; 122(8): 1184 - 1191.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
O. Cuvier, S. Stanojcic, J.-M. Lemaitre, and M. Mechali
A topoisomerase II-dependent mechanism for resetting replicons at the S-M-phase transition
Genes & Dev., April 1, 2008; 22(7): 860 - 865.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I. Radichev, S. W. Kwon, Y. Zhao, M. L. DePamphilis, and A. Vassilev
Genetic Analysis of Human Orc2 Reveals Specific Domains That Are Required in Vivo for Assembly and Nuclear Localization of the Origin Recognition Complex
J. Biol. Chem., August 11, 2006; 281(32): 23264 - 23273.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2006