TopBP1 activates the ATR-ATRIP complex

Cell
Akiko KumagaiWilliam G Dunphy

Abstract

ATR is a key regulator of checkpoint responses to incompletely replicated and damaged DNA, but the mechanisms underlying control of its kinase activity are unknown. TopBP1, the vertebrate homolog of yeast Cut5/Dbp11, has dual roles in initiation of DNA replication and regulation of checkpoint responses. We show that recombinant TopBP1 induces a large increase in the kinase activity of both Xenopus and human ATR. The ATR-activating domain resides in a conserved segment of TopBP1 that is distinct from its numerous BRCT repeats. The isolated ATR-activating domain from TopBP1 induces ectopic activation of ATR-dependent signaling in both Xenopus egg extracts and human cells. Furthermore, Xenopus egg extracts containing a version of TopBP1 with an inactivating point mutation in the ATR-activating domain are defective in checkpoint regulation. These studies establish that activation of ATR by TopBP1 is a crucial step in the initiation of ATR-dependent signaling processes.

References

Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·H ArakiA Sugino
Jan 1, 1997·Annual Review of Cell and Developmental Biology·D O Morgan
Jun 8, 2001·Molecular and Cellular Biology·H Zhao, H Piwnica-Worms
Jun 8, 2001·The Journal of Biological Chemistry·M MäkiniemiJ E Syväoja
Aug 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·P NghiemS L Schreiber
Sep 7, 2001·Genes & Development·R T Abraham
Nov 21, 2001·The Journal of Biological Chemistry·Yoshiomi HondaMitsuyoshi Nakao
Nov 27, 2001·Science·D CortezS J Elledge
Jan 5, 2002·Molecular and Cellular Biology·Kazuhiko YamaneJunjie Chen
May 17, 2002·The Journal of Biological Chemistry·Zhongsheng YouJohn Newport
Sep 6, 2002·The Journal of Cell Biology·Matthew P StokesW Matthew Michael
Sep 17, 2002·Genes & Development·Patrick J LupardusKarlene A Cimprich
Nov 14, 2002·Annual Review of Genetics·Kara A NybergTed A Weinert
Nov 20, 2002·The Journal of Cell Biology·Ruth A Van HattenW Matthew Michael
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
May 14, 2003·The EMBO Journal·Yoshitami Hashimoto, Haruhiko Takisawa
May 27, 2003·The Journal of Biological Chemistry·Claudia Christiano Silva Chini, Junjie Chen
Jun 7, 2003·Science·Lee Zou, Stephen J Elledge
Jun 20, 2003·Current Biology : CB·Christine E Canman
Oct 4, 2003·The Journal of Biological Chemistry·Edgardo R Parrilla-Castellar, Larry M Karnitz
Jan 20, 2004·Molecular and Cellular Biology·Keziban Unsal-Kaçmaz, Aziz Sancar
Apr 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Shiaw-Yih LinStephen J Elledge
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·David CortezStephen J Elledge
Jul 10, 2004·Cell·Christopher J Bakkenist, Michael B Kastan
Sep 17, 2004·The Journal of Biological Chemistry·Akiko KumagaiWilliam G Dunphy
Sep 28, 2004·The Journal of Biological Chemistry·Hae Yong YooWilliam G Dunphy
May 18, 2005·DNA Repair·Valerie GarciaAntony M Carr
Jul 20, 2005·The Journal of Biological Chemistry·Heather L Ball, David Cortez
Sep 17, 2005·Nature Reviews. Molecular Cell Biology·Haico van Attikum, Susan M Gasser

❮ Previous
Next ❯

Citations

Dec 17, 2009·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Makoto NakanishiMidori Shimada
May 1, 2012·Molecular Biology Reports·Ewa FormaMagdalena Brys
Jul 27, 2007·Cell Biochemistry and Biophysics·Laura R BarkleyCyrus Vaziri
Nov 27, 2008·Cell Biochemistry and Biophysics·Magda Budzowska, Roland Kanaar
Aug 3, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hyuk-Jin Cha, Hyungshin Yim
Nov 1, 2008·Cell Death and Differentiation·D Sombroek, T G Hofmann
Oct 30, 2013·Nature Neuroscience·Peter J McKinnon
Jun 25, 2008·Nature Reviews. Cancer·Fabrizio d'Adda di Fagagna
May 23, 2009·Nature Reviews. Cancer·Steffi HeroldMartin Eilers
Jul 3, 2008·Nature Reviews. Molecular Cell Biology·Karlene A Cimprich, David Cortez
Sep 24, 2010·Nature Reviews. Molecular Cell Biology·Marcel Méchali
Aug 24, 2013·Nature Reviews. Molecular Cell Biology·H Christian Reinhardt, Michael B Yaffe
May 10, 2011·Nature Structural & Molecular Biology·Luis I ToledoOscar Fernandez-Capetillo
Oct 29, 2008·Oncogene·B EwaldW Plunkett
Nov 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Daniel A MordesDavid Cortez
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Khamilia BedelbaevaEllen Heber-Katz
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jun-Hyuk ChoiAziz Sancar
Jul 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yong-jie Xu, Michael Leffak
May 22, 2009·The Journal of Biological Chemistry·Sheng-Hong Chen, Huilin Zhou
Dec 24, 2009·The Journal of Biological Chemistry·Yiyong LiuPaul Modrich
Mar 18, 2010·The Journal of Biological Chemistry·Michael G KempKeziban Unsal-Kaçmaz
Apr 24, 2010·The Journal of Biological Chemistry·Ruifeng GuoDavid G Johnson
May 13, 2011·The Journal of Biological Chemistry·Ming YueYong-jie Xu
Jun 28, 2011·The Journal of Biological Chemistry·Edward A NamDavid Cortez
May 15, 2009·The Journal of Biological Chemistry·Naoko Yoshizawa-Sugata, Hisao Masai
Oct 17, 2008·The Journal of Biological Chemistry·Vasundhara M Navadgi-Patil, Peter M Burgers
May 26, 2006·Molecular Biology of the Cell·Lorena Taricani, Teresa S F Wang
Mar 13, 2009·Molecular Biology of the Cell·Hae Yong YooWilliam G Dunphy
May 30, 2009·Molecular Biology of the Cell·Ali PedramEllis R Levin
Sep 15, 2009·Carcinogenesis·Po-Chen ChuMau-Sun Chang
Oct 2, 2009·Carcinogenesis·William K Kaufmann
Jan 14, 2009·Nucleic Acids Research·Jun-Hyuk ChoiAziz Sancar
Nov 27, 2010·Nucleic Acids Research·Diane M Kanter, Daniel L Kaplan
Aug 21, 2010·Nucleic Acids Research·Mathieu RappasLaurence H Pearl
Dec 22, 2011·Nucleic Acids Research·Bénédicte RecolinDomenico Maiorano
Feb 10, 2012·Nucleic Acids Research·Charles VadnaisAlain Nepveu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

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.