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
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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
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Somatic and gynecological status of reproductive-age of women with benign tumors and tumor-like formations of the ovaries
TL;DR: It is claimed that £1.3bn will be spent on refurbishing the Titanic's hull during World War II due to damage caused by the explosion.
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Dynamic Reorganization of the Cytoskeleton during Apoptosis: The Two Coffins Hypothesis.
Suleva Povea-Cabello,Manuel Oropesa-Ávila,Patricia de la Cruz-Ojeda,Marina Villanueva-Paz,Mario de la Mata,Juan M. Suárez-Rivero,Mónica Álvarez-Córdoba,Irene Villalón-García,David Cotán,Patricia Ybot-Gonzalez,José Antonio Sánchez-Alcázar +10 more
TL;DR: Round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocyte responses, suggesting that knowing the type of apoptosis may be important to predict how fast apoptotic cells undergo secondary necrosis and the subsequent immune response.
Journal ArticleDOI
The cellular phenotype of Roberts syndrome fibroblasts as revealed by ectopic expression of ESCO2.
Petra van der Lelij,Barbara C. Godthelp,Wouter van Zon,Djoke van Gosliga,Anneke B. Oostra,Jurgen Steltenpool,Jan de Groot,Rik J. Scheper,Rob M. F. Wolthuis,Quinten Waisfisz,Firouz Darroudi,Hans Joenje,Johan P. de Winter +12 more
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Journal ArticleDOI
Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination.
Chloé Lescale,Hélène Lenden Hasse,Andrew N. Blackford,Andrew N. Blackford,Andrew N. Blackford,Gabriel Balmus,Gabriel Balmus,Joy J. Bianchi,Joy J. Bianchi,Wei Yu,Léa Bacoccina,Angélique Jarade,Christophe Clouin,Rohan Sivapalan,Bernardo Reina-San-Martin,Stephen P. Jackson,Stephen P. Jackson,Ludovic Deriano +17 more
TL;DR: The role of PAXX in V(D)J recombination is illuminated and support a model in which PAXX and XLF function during NHEJ repair of DNA breaks, whereas XLF, the RAG complex, and the ATM-dependent DNA damage response promote end joining by stabilizing DNA ends.
Journal ArticleDOI
Testicular cancer: Determinants of cisplatin sensitivity and novel therapeutic opportunities.
TL;DR: Pre-clinical successes with chemotherapy and targeted drug combinations fuel the need for further investigation in clinical setting, and patient-derived xenograft models hold potential for mechanistic studies and pre-clinical validation of novel therapeutic strategies in TC.
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.