Direct requirement for Xmus101 in ATR-mediated phosphorylation of Claspin bound Chk1 during checkpoint signaling.

The Journal of Cell Biology
Shan YanW Matthew Michael

Abstract

TopBP1-like proteins, which include Xenopus laevis Xmus101, are required for DNA replication and have been linked to replication checkpoint control. A direct role for TopBP1/Mus101 in checkpoint control has been difficult to prove, however, because of the requirement for replication in generating the DNA structures that activate the checkpoint. Checkpoint activation occurs in X. laevis egg extracts upon addition of an oligonucleotide duplex (AT70). We show that AT70 bypasses the requirement for replication in checkpoint activation. We take advantage of this replication-independent checkpoint system to determine the role of Xmus101 in the checkpoint. We find that Xmus101 is essential for AT70-mediated checkpoint signaling and that it functions to promote phosphorylation of Claspin bound Chk1 by the ataxia-telangiectasia and Rad-3-related (ATR) protein kinase. We also identify a separation-of-function mutant of Xmus101. In extracts expressing this mutant, replication of sperm chromatin occurs normally; however, the checkpoint response to stalled replication forks fails. These data demonstrate that Xmus101 functions directly during signal relay from ATR to Chk1.

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Citations

Jul 3, 2008·Nature Reviews. Molecular Cell Biology·Karlene A Cimprich, David Cortez
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jun-Hyuk ChoiAziz Sancar
Jun 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jeremy WillisShan Yan
Jan 14, 2009·Nucleic Acids Research·Jun-Hyuk ChoiAziz Sancar
Jun 4, 2008·Genes & Development·Daniel A MordesDavid Cortez
Jan 19, 2010·Genes & Development·Christopher L SansamJacqueline A Lees
Aug 2, 2006·Molecular and Cellular Biology·Shizhou LiuJiri Lukas
Jun 30, 2006·Annual Review of Genetics·Jacob C Harrison, James E Haber
Oct 19, 2012·Cell Division·Zhen Shen, Supriya G Prasanth
Nov 15, 2012·Journal of Visualized Experiments : JoVE·Jeremy WillisShan Yan
Apr 8, 2014·Genes·Bénédicte RecolinDomenico Maiorano
Aug 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jun-Hyuk ChoiAziz Sancar
Jun 21, 2014·Cellular and Molecular Life Sciences : CMLS·Shan YanZachary Berman
Mar 18, 2009·The Journal of Cell Biology·Shan Yan, W Matthew Michael
Apr 14, 2010·The Journal of Cell Biology·Christopher VanKarlene A Cimprich
Aug 23, 2006·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yoshitami HashimotoHaruhiko Takisawa
Aug 5, 2014·DNA Repair·Christopher P WardlawAntony W Oliver
Jul 14, 2010·Current Biology : CB·Yu V Fu, Johannes C Walter
Jan 22, 2013·Biochemical and Biophysical Research Communications·Shan Yan, Jeremy Willis
Mar 24, 2007·DNA Repair·Hélène Tourrière, Philippe Pasero
Jan 24, 2018·Nucleic Acids Research·Yunfeng LinShan Yan
Jul 20, 2007·The Journal of Biological Chemistry·Joon LeeWilliam G Dunphy
May 23, 2013·The Journal of Biological Chemistry·Bachar H HassanAziz Sancar
Dec 29, 2016·Proceedings of the National Academy of Sciences of the United States of America·Bret D WallaceR Scott Williams
Dec 15, 2010·The Journal of Biological Chemistry·Yoon JeonDeog Su Hwang
Jul 25, 2018·The Journal of Biological Chemistry·Sumeet PoudelMichael Leffak
Apr 21, 2007·The Journal of Biological Chemistry·Hae Yong YooWilliam G Dunphy
Sep 29, 2020·DNA Repair·Ahhyun KimW Matthew Michael

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Methods Mentioned

BETA
immunodepletion
interaction assay
affinity purification

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