Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast.

Genes & Development
Yong-jie XuThomas J Kelly

Abstract

The DNA replication checkpoint is a complex signal transduction pathway, present in all eukaryotic cells, that functions to maintain genomic integrity and cell viability when DNA replication is perturbed. In Schizosaccharomyces pombe the major effector of the replication checkpoint is the protein kinase Cds1. Activation of Cds1 is known to require the upstream kinase Rad3 and the mediator Mrc1, but the biochemical mechanism of activation is not well understood. We report that the replication checkpoint is activated in two stages. In the first stage, Mrc1 recruits Cds1 to stalled replication forks by interactions between the FHA domain of Cds1 and specific phosphorylated Rad3 consensus sites in Mrc1. Cds1 is then primed for activation by Rad3-dependent phosphorylation. In the second stage, primed Cds1 molecules dimerize via phospho-specific interactions mediated by the FHA domains and are activated by autophosphorylation. This two-stage activation mechanism for the replication checkpoint allows for rapid activation with a high signal-to-noise ratio.

References

Nov 12, 1993·Science·D M SpencerG R Crabtree
May 23, 1998·Science·M N BoddyP Russell
Dec 19, 1998·The EMBO Journal·R G MartinhoN J Bentley
Oct 13, 1999·Molecular Cell·D DurocherS P Jackson
Aug 31, 2000·Annual Review of Biochemistry·T J Kelly, G W Brown
Oct 12, 2000·Molecular and Cellular Biology·H A SnaithS L Forsburg
Aug 21, 2001·Molecular Cell·C S GilbertN F Lowndes
Nov 21, 2001·Nature Cell Biology·A A AlcasabasS J Elledge
Nov 21, 2001·Nature Cell Biology·K Tanaka, P Russell
Dec 1, 2001·Current Biology : CB·M N Boddy, P Russell
Feb 21, 2002·Molecular Biology of the Cell·Tom D Wolkow, Tamar Enoch
Mar 26, 2002·FEBS Letters·Daniel Durocher, Stephen P Jackson
May 25, 2002·Molecular and Cellular Biology·Xingzhi XuDavid F Stern
Jun 5, 2002·Annual Review of Biochemistry·Stephen P Bell, Anindya Dutta
Nov 14, 2002·Annual Review of Genetics·Kara A NybergTed A Weinert
Nov 26, 2002·Trends in Cell Biology·Alexander J OsbornLee Zou
Jan 25, 2003·Nature Cell Biology·Akiko Kumagai, William G Dunphy
Feb 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·Vladimir P BermudezAziz Sancar
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jerzy Majka, Peter M J Burgers
Jun 7, 2003·Science·Lee Zou, Stephen J Elledge
Aug 5, 2003·Molecular and Cellular Biology·Michael N BoddyPaul Russell
Sep 4, 2003·Journal of Cell Science·Kanji Furuya, Antony M Carr
Oct 31, 2003·Molecular and Cellular Biology·Hui ZhaoPaul Russell
Dec 4, 2003·Mutation Research·Bernard P Duncker, Grant W Brown
Jun 3, 2004·The Journal of Biological Chemistry·Katsunori Tanaka, Paul Russell
Jul 29, 2004·DNA Repair·Jinwoo AhnCarol Prives
Oct 9, 2004·The Journal of Biological Chemistry·Hui Zhao, Paul Russell
Apr 15, 2005·Nature·Vassilis G GorgoulisThanos D Halazonetis
Aug 9, 2005·Current Biology : CB·Frédéric D SweeneyDaniel Durocher

❮ Previous
Next ❯

Citations

Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Naoki NitaniTakuro Nakagawa
May 22, 2009·The Journal of Biological Chemistry·Sheng-Hong Chen, Huilin Zhou
May 13, 2011·The Journal of Biological Chemistry·Ming YueYong-jie Xu
Nov 23, 2006·The Journal of Biological Chemistry·Sheng-hong ChenHuilin Zhou
Apr 10, 2009·The Journal of Biological Chemistry·Yong-Jie Xu, Thomas J Kelly
Aug 1, 2008·Molecular Biology of the Cell·Ling YinGennaro D'Urso
Nov 28, 2008·Molecular Biology of the Cell·Nicholas Willis, Nicholas Rhind
Jan 27, 2012·Genes & Development·Motoshi HayanoHisao Masai
Oct 10, 2012·Molecular and Cellular Biology·Sarah A SabatinosSusan L Forsburg
Apr 27, 2011·Molecular and Cellular Biology·Motoshi HayanoHisao Masai
Mar 1, 2012·Journal of Cell Science·Kirstin L BassMatthew J O'Connell
Apr 10, 2012·Annual Review of Biochemistry·Jane A EndicottLouise N Johnson
Feb 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Takehiko Usui, John H J Petrini
Dec 15, 2010·Bioscience, Biotechnology, and Biochemistry·Katsunori Tanaka
Jul 14, 2007·Trends in Biochemical Sciences·Antony W OliverLaurence H Pearl
Oct 21, 2006·The EMBO Journal·Christian HeichingerPaul Nurse
Jun 24, 2006·The EMBO Journal·Antony W OliverLaurence H Pearl
Apr 2, 2014·Seminars in Cell & Developmental Biology·Juergen Zech, Jacob Zeuthen Dalgaard
Apr 6, 2017·The Journal of Biological Chemistry·Amanpreet Singh, Yong-Jie Xu
Mar 31, 2017·Current Genetics·Hisao MasaiSeiji Matsumoto
Jan 11, 2017·Molecular and Cellular Biology·Seiji MatsumotoHisao Masai
Dec 19, 2018·Genes·Seong Min Kim, Susan L Forsburg
Dec 13, 2007·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Nov 24, 2018·Current Genetics·María Moriel-CarreteroBenjamin Pardo
May 31, 2014·G3 : Genes - Genomes - Genetics·Lin Ding, Susan L Forsburg
Apr 29, 2020·Molecular and Cellular Biology·Seong Min Kim, Susan L Forsburg
Jan 23, 2008·Biochemical Society Transactions·Susan L Forsburg

❮ 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.