Phosphorylation of ORC2 protein dissociates origin recognition complex from chromatin and replication origins.

The Journal of Biological Chemistry
Kyung Yong LeeDeog Su Hwang

Abstract

During the late M to the G(1) phase of the cell cycle, the origin recognition complex (ORC) binds to the replication origin, leading to the assembly of the prereplicative complex for subsequent initiation of eukaryotic chromosome replication. We found that the cell cycle-dependent phosphorylation of human ORC2, one of the six subunits of ORC, dissociates ORC2, -3, -4, and -5 (ORC2-5) subunits from chromatin and replication origins. Phosphorylation at Thr-116 and Thr-226 of ORC2 occurs by cyclin-dependent kinase during the S phase and is maintained until the M phase. Phosphorylation of ORC2 at Thr-116 and Thr-226 dissociated the ORC2-5 from chromatin. Consistent with this, the phosphomimetic ORC2 protein exhibited defective binding to replication origins as well as to chromatin, whereas the phosphodefective protein persisted in binding throughout the cell cycle. These results suggest that the phosphorylation of ORC2 dissociates ORC from chromatin and replication origins and inhibits binding of ORC to newly replicated DNA.

References

Apr 1, 1993·Genes & Development·M BraunsteinJ R Broach
Jan 1, 1997·Annual Review of Cell and Developmental Biology·A Dutta, S P Bell
Sep 15, 1999·Proceedings of the National Academy of Sciences of the United States of America·A WoetmannN Odum
Apr 5, 2000·The Journal of Biological Chemistry·Y IshimiM Kitagawa
Dec 5, 2000·The Journal of Biological Chemistry·S KreitzR Knippers
Apr 27, 2001·The Journal of Biological Chemistry·S VasheeT J Kelly
May 11, 2001·The Journal of Biological Chemistry·L M DelmolinoA Dutta
Aug 4, 2001·Molecular and Cellular Biology·A VasJ Leatherwood
Nov 22, 2001·Experimental Cell Research·H LamanN Jones
Jun 5, 2002·Annual Review of Biochemistry·Stephen P Bell, Anindya Dutta
Aug 12, 2003·The Journal of Biological Chemistry·Satoshi OhtaChikashi Obuse
Aug 12, 2003·The Journal of Biological Chemistry·Yasutoshi TatsumiChikashi Obuse
Mar 3, 2004·The Journal of Biological Chemistry·Nozomi SugimotoMasatoshi Fujita
Sep 24, 2004·Current Biology : CB·John F X Diffley
Dec 22, 2004·Cell Cycle·Melvin L DePamphilis
Dec 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jennifer Giordano-ColtartJerard Hurwitz
Jun 2, 2005·Nature Reviews. Molecular Cell Biology·J Julian Blow, Anindya Dutta
Mar 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Anand Ranjan, Manfred Gossen
May 3, 2006·Current Opinion in Cell Biology·Melvin L DePamphilisAlex Vassilev
Sep 7, 2006·Molecular and Cellular Biology·Jeannine GerhardtAloys Schepers
Mar 9, 2007·Genes & Development·Emily E Arias, Johannes C Walter
Jun 23, 2007·Nature Reviews. Molecular Cell Biology·Jeffrey A Ubersax, James E Ferrell
Jul 17, 2007·Annual Review of Genetics·R A Sclafani, T M Holzen
Aug 25, 2007·The Journal of Biological Chemistry·Khalid Siddiqui, Bruce Stillman
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Cecile EvrinChristian Speck
Jan 26, 2010·The Journal of Biological Chemistry·Vasiliki Tsakraklides, Stephen P Bell
Feb 4, 2011·Genes & Development·Shuyan Chen, Stephen P Bell

❮ Previous
Next ❯

Citations

Feb 13, 2013·Molecular and Cellular Biology·Jonghoon ParkAnindya Dutta
May 6, 2014·Biochemical and Biophysical Research Communications·Kyung Yong LeeDeog Su Hwang
Jan 29, 2016·Nature Communications·David WalterClaus Storgaard Sørensen
Jan 19, 2016·Current Genetics·Abhijit S DeshmukhSuman Kumar Dhar
Oct 11, 2015·Cell and Tissue Research·Michael A OrtegaW Steven Ward
Oct 29, 2014·Development, Growth & Differentiation·Shin MuraiShigeru Yamashita
Apr 16, 2014·Biochemical and Biophysical Research Communications·Kyung Yong LeeDeog Su Hwang
May 23, 2014·Current Biology : CB·Stephanie A Hills, John F X Diffley
Apr 1, 2014·Molecular and Biochemical Parasitology·Simone CalderanoM Carolina Elias
Jan 27, 2017·Genes·Alex Vassilev, Melvin L DePamphilis
Sep 27, 2019·FEBS Letters·Juanita C Limas, Jeanette Gowen Cook
Oct 21, 2017·Oncotarget·Ronghua WangChao Huang
Oct 13, 2020·Cell Cycle·Rosaline Y C HsuSupriya G Prasanth

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.