Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance

<p>Silencing of SMG1 resensitizes SMG8 and SMG9 knockout cells to ATR inhibition. <b>A,</b> Left, SMG1 was overexpressed in the SMG8 and SMG9 mutant cells after 48 hours of DMSO or 150 nmol/L berzosertib exposure compared with the WT cells. Right, Smg1 signal intensity relative to...

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Yazar: Marta J. Llorca-Cardenosa (14961612) (author)
Diğer Yazarlar: Lauren I. Aronson (14961615) (author), Dragomir B. Krastev (14961618) (author), Jadwiga Nieminuszczy (14961621) (author), John Alexander (14961624) (author), Feifei Song (14961627) (author), Malgorzata Dylewska (14961630) (author), Ronan Broderick (14961633) (author), Rachel Brough (14961636) (author), Astrid Zimmermann (14961639) (author), Frank T. Zenke (14961642) (author), Bora Gurel (14961645) (author), Ruth Riisnaes (14961648) (author), Ana Ferreira (14961651) (author), Theodoros Roumeliotis (14961654) (author), Jyoti Choudhary (14961657) (author), Stephen J. Pettitt (14952601) (author), Johann de Bono (14961660) (author), Andres Cervantes (14961663) (author), Syed Haider (14961666) (author), Wojciech Niedzwiedz (14961669) (author), Christopher J. Lord (14952616) (author), Irene Y. Chong (14961672) (author)
Baskı/Yayın Bilgisi: 2025
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author Marta J. Llorca-Cardenosa (14961612)
author2 Lauren I. Aronson (14961615)
Dragomir B. Krastev (14961618)
Jadwiga Nieminuszczy (14961621)
John Alexander (14961624)
Feifei Song (14961627)
Malgorzata Dylewska (14961630)
Ronan Broderick (14961633)
Rachel Brough (14961636)
Astrid Zimmermann (14961639)
Frank T. Zenke (14961642)
Bora Gurel (14961645)
Ruth Riisnaes (14961648)
Ana Ferreira (14961651)
Theodoros Roumeliotis (14961654)
Jyoti Choudhary (14961657)
Stephen J. Pettitt (14952601)
Johann de Bono (14961660)
Andres Cervantes (14961663)
Syed Haider (14961666)
Wojciech Niedzwiedz (14961669)
Christopher J. Lord (14952616)
Irene Y. Chong (14961672)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Marta J. Llorca-Cardenosa (14961612)
Lauren I. Aronson (14961615)
Dragomir B. Krastev (14961618)
Jadwiga Nieminuszczy (14961621)
John Alexander (14961624)
Feifei Song (14961627)
Malgorzata Dylewska (14961630)
Ronan Broderick (14961633)
Rachel Brough (14961636)
Astrid Zimmermann (14961639)
Frank T. Zenke (14961642)
Bora Gurel (14961645)
Ruth Riisnaes (14961648)
Ana Ferreira (14961651)
Theodoros Roumeliotis (14961654)
Jyoti Choudhary (14961657)
Stephen J. Pettitt (14952601)
Johann de Bono (14961660)
Andres Cervantes (14961663)
Syed Haider (14961666)
Wojciech Niedzwiedz (14961669)
Christopher J. Lord (14952616)
Irene Y. Chong (14961672)
author_role author
dc.creator.none.fl_str_mv Marta J. Llorca-Cardenosa (14961612)
Lauren I. Aronson (14961615)
Dragomir B. Krastev (14961618)
Jadwiga Nieminuszczy (14961621)
John Alexander (14961624)
Feifei Song (14961627)
Malgorzata Dylewska (14961630)
Ronan Broderick (14961633)
Rachel Brough (14961636)
Astrid Zimmermann (14961639)
Frank T. Zenke (14961642)
Bora Gurel (14961645)
Ruth Riisnaes (14961648)
Ana Ferreira (14961651)
Theodoros Roumeliotis (14961654)
Jyoti Choudhary (14961657)
Stephen J. Pettitt (14952601)
Johann de Bono (14961660)
Andres Cervantes (14961663)
Syed Haider (14961666)
Wojciech Niedzwiedz (14961669)
Christopher J. Lord (14952616)
Irene Y. Chong (14961672)
dc.date.none.fl_str_mv 2025-11-24T22:40:24Z
dc.identifier.none.fl_str_mv 10.1158/0008-5472.30699136
dc.relation.none.fl_str_mv https://figshare.com/articles/figure/Figure_3_from_SMG8_SMG9_Heterodimer_Loss_Modulates_SMG1_Kinase_to_Drive_ATR_Inhibitor_Resistance/30699136
dc.rights.none.fl_str_mv CC BY
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Cancer
Molecular and Cellular Biology
Therapeutic Research and Development
DNA Damage and Repair
DNA repair
Drug Mechanisms
Drug Resistance
Gastrointestinal Cancers
Stomach cancer
dc.title.none.fl_str_mv Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
dc.type.none.fl_str_mv Image
Figure
info:eu-repo/semantics/publishedVersion
image
description <p>Silencing of SMG1 resensitizes SMG8 and SMG9 knockout cells to ATR inhibition. <b>A,</b> Left, SMG1 was overexpressed in the SMG8 and SMG9 mutant cells after 48 hours of DMSO or 150 nmol/L berzosertib exposure compared with the WT cells. Right, Smg1 signal intensity relative to β-actin expression representing relative protein expression using ImageJ. Error bars represent SEM, considering three biological replicates. <b>B</b> and <b>C,</b> SMG1 knockdown experiment (384-well plates) showing an increase in the normalized percent of inhibition in the SMG8 and SMG9 mutant cells (red) compared with the WT cells (blue) following exposure to a range of SMG1 siRNA concentrations (from 1 to 20 nmol/L; negative controls, siCON1, siCON2; positive controls, siATM, siPLK1). <b>D,</b> Western blot analysis showing siSMG1 silencing in the YCC6 WT and SMG8 and SMG9 mutant cells. <b>E–G,</b> Silencing of SMG1 in YCC6 WT, SMG8, and SMG9 mutant cells resensitizes them to ATRi (384-well plate, 5-day assay). siCON2 was used as a negative control. All panels of this figure are representative of three or more biological replicates. ns, nonsignificant.</p>
eu_rights_str_mv openAccess
id Manara_394c064207e5c4ee928953f745d0340c
identifier_str_mv 10.1158/0008-5472.30699136
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/30699136
publishDate 2025
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY
spelling Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor ResistanceMarta J. Llorca-Cardenosa (14961612)Lauren I. Aronson (14961615)Dragomir B. Krastev (14961618)Jadwiga Nieminuszczy (14961621)John Alexander (14961624)Feifei Song (14961627)Malgorzata Dylewska (14961630)Ronan Broderick (14961633)Rachel Brough (14961636)Astrid Zimmermann (14961639)Frank T. Zenke (14961642)Bora Gurel (14961645)Ruth Riisnaes (14961648)Ana Ferreira (14961651)Theodoros Roumeliotis (14961654)Jyoti Choudhary (14961657)Stephen J. Pettitt (14952601)Johann de Bono (14961660)Andres Cervantes (14961663)Syed Haider (14961666)Wojciech Niedzwiedz (14961669)Christopher J. Lord (14952616)Irene Y. Chong (14961672)CancerMolecular and Cellular BiologyTherapeutic Research and DevelopmentDNA Damage and RepairDNA repairDrug MechanismsDrug ResistanceGastrointestinal CancersStomach cancer<p>Silencing of SMG1 resensitizes SMG8 and SMG9 knockout cells to ATR inhibition. <b>A,</b> Left, SMG1 was overexpressed in the SMG8 and SMG9 mutant cells after 48 hours of DMSO or 150 nmol/L berzosertib exposure compared with the WT cells. Right, Smg1 signal intensity relative to β-actin expression representing relative protein expression using ImageJ. Error bars represent SEM, considering three biological replicates. <b>B</b> and <b>C,</b> SMG1 knockdown experiment (384-well plates) showing an increase in the normalized percent of inhibition in the SMG8 and SMG9 mutant cells (red) compared with the WT cells (blue) following exposure to a range of SMG1 siRNA concentrations (from 1 to 20 nmol/L; negative controls, siCON1, siCON2; positive controls, siATM, siPLK1). <b>D,</b> Western blot analysis showing siSMG1 silencing in the YCC6 WT and SMG8 and SMG9 mutant cells. <b>E–G,</b> Silencing of SMG1 in YCC6 WT, SMG8, and SMG9 mutant cells resensitizes them to ATRi (384-well plate, 5-day assay). siCON2 was used as a negative control. All panels of this figure are representative of three or more biological replicates. ns, nonsignificant.</p>2025-11-24T22:40:24ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1158/0008-5472.30699136https://figshare.com/articles/figure/Figure_3_from_SMG8_SMG9_Heterodimer_Loss_Modulates_SMG1_Kinase_to_Drive_ATR_Inhibitor_Resistance/30699136CC BYinfo:eu-repo/semantics/openAccessoai:figshare.com:article/306991362025-11-24T22:40:24Z
spellingShingle Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
Marta J. Llorca-Cardenosa (14961612)
Cancer
Molecular and Cellular Biology
Therapeutic Research and Development
DNA Damage and Repair
DNA repair
Drug Mechanisms
Drug Resistance
Gastrointestinal Cancers
Stomach cancer
status_str publishedVersion
title Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
title_full Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
title_fullStr Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
title_full_unstemmed Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
title_short Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
title_sort Figure 3 from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
topic Cancer
Molecular and Cellular Biology
Therapeutic Research and Development
DNA Damage and Repair
DNA repair
Drug Mechanisms
Drug Resistance
Gastrointestinal Cancers
Stomach cancer