Journal ArticleDOI
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
Shuhei Matsuoka,Bryan A. Ballif,Agata Smogorzewska,Agata Smogorzewska,E. Robert McDonald,Kristen E. Hurov,Ji Luo,Corey E. Bakalarski,Zhenming Zhao,Nicole L. Solimini,Yaniv Lerenthal,Yosef Shiloh,Steven P. Gygi,Stephen J. Elledge +13 more
TLDR
A large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR is performed and more than 900 regulated phosphorylation sites encompassing over 700 proteins are identified.Abstract:
Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related). The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage response (DDR). We performed a large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins. Functional analysis of a subset of this data set indicated that this list is highly enriched for proteins involved in the DDR. This set of proteins is highly interconnected, and we identified a large number of protein modules and networks not previously linked to the DDR. This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals.read more
Citations
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Pfetin as a Prognostic Biomarker of Gastrointestinal Stromal Tumors Revealed by Proteomics
Yoshiyuki Suehara,Tadashi Kondo,Kunihiko Seki,Tatsuhiro Shibata,Kiyonaga Fujii,Masahiro Gotoh,Tadashi Hasegawa,Yasuhiro Shimada,Mitsuru Sasako,Tadakazu Shimoda,Hisashi Kurosawa,Yasuo Beppu,Akira Kawai,Setsuo Hirohashi +13 more
TL;DR: Pfetin expression was a powerful prognostic factor among the clinicopathologic variables examined, including risk classification and c-kit– or platelet-derived growth factor receptor A mutation status, and may provide novel therapeutic strategies to prevent metastasis of GIST.
Journal ArticleDOI
Heat Shock Protein 90α (Hsp90α) Is Phosphorylated in Response to DNA Damage and Accumulates in Repair Foci
Maria Quanz,Aurélie Herbette,Mano Sayarath,Leanne De Koning,Thierry Dubois,Jian-Sheng Sun,Marie Dutreix +6 more
TL;DR: The threonine 7 (Thr-7) residue of heat shock protein 90α (Hsp90α) was phosphorylated immediately after DNA damage and may serve as a surrogate biomarker of DNA damage, shedding light on the interplay between central DNA repair enzymes and an essential molecular chaperone.
Journal ArticleDOI
The Arabidopsis COP9 signalosome is essential for G2 phase progression and genomic stability
Esther M.N. Dohmann,Mitchell P. Levesque,Lieven De Veylder,Lieven De Veylder,Ilka Reichardt,Gerd Jürgens,Markus Schmid,Claus Schwechheimer +7 more
TL;DR: The COP9 signalosome (CSN) is required for the full activity of cullin-RING E3 ubiquitin ligases (CRLs) in eukaryotes as mentioned in this paper.
Journal ArticleDOI
Wolf–Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage
TL;DR: It is reported that the WHSC1 protein is a member of the DDR pathway and is required for resistance to many DNA-damaging and replication stress-inducing agents.
Journal ArticleDOI
DNA Damage Activates the SAC in an ATM/ATR-Dependent Manner, Independently of the Kinetochore
Eun Mi Kim,Daniel J. Burke +1 more
TL;DR: This work shows that yeast cells lacking the DNA damage checkpoint arrest prior to anaphase in response to low doses of the DNA damaging agent methyl methane sulfonate (MMS) and suggests that there are novel, important targets of ATM and ATR for cell cycle regulation.
References
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Journal ArticleDOI
The DNA damage response: putting checkpoints in perspective
TL;DR: The inability to repair DNA damage properly in mammals leads to various disorders and enhanced rates of tumour development, and this work has shown that direct activation of DNA repair networks is needed to correct this problem.
Journal ArticleDOI
Cell-cycle checkpoints and cancer
Michael B. Kastan,Jiri Bartek +1 more
TL;DR: All life on earth must cope with constant exposure to DNA-damaging agents such as the Sun's radiation, and how cells respond to DNA damage are critical determinants of whether that individual will develop cancer.
Journal ArticleDOI
DNA damage-induced activation of p53 by the checkpoint kinase Chk2.
Atsushi Hirao,Young-Yun Kong,Shuhei Matsuoka,Andrew Wakeham,Jürgen Ruland,Hiroki Yoshida,Dou Liu,Stephen J. Elledge,Tak W. Mak +8 more
TL;DR: Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding, and provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage.
Journal ArticleDOI
Immunoaffinity profiling of tyrosine phosphorylation in cancer cells
John Rush,Albrecht Moritz,Kimberly Lee,Ailan Guo,Valerie Goss,Erik Spek,Hui Zhang,Hui Zhang,Hui Zhang,Xiang-ming Zha,Xiang-ming Zha,Xiang-ming Zha,Roberto D. Polakiewicz,Michael J. Comb +13 more
TL;DR: Applying this approach to several cell systems, including cancer cell lines, shows it can be used to identify activated protein kinases and their phosphorylated substrates without prior knowledge of the signaling networks that are activated, a first step in profiling normal and oncogenic signaling networks.
Journal Article
Global Analysis of Protein Phosphorylation in Yeast
Jason Ptacek,Geeta Devgan,Gregory A. Michaud,Heng Zhu,Xiaowei Zhu,Joseph Fasolo,Hong Guo,Ghil Jona,Ashton Breitkreutz,Richelle Sopko,Rhonda R. McCartney,Martin C. Schmidt,Najma Rachidi,Soo-Jung Lee,Angie S. Mah,Lihao Meng,Michael J. R. Stark,David F. Stern,Claudio De Virgilio,Mike Tyers,Brenda J. Andrews,Mark Gerstein,Barry Schweitzer,Paul F. Predki,Michael Snyder +24 more
TL;DR: The in vitro substrates recognized by most yeast protein kinases are described, with the use of proteome chip technology, and these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.