دورية أكاديمية
Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial
| العنوان: | Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial |
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| المؤلفون: | Roisné-Hamelin, Florian, Pobiega, Sabrina, Jézéquel, Kévin, Miron, Simona, Dépagne, Jordane, Veaute, Xavier, Busso, Didier, Du, Marie-Hélène Le, Callebaut, Isabelle, Charbonnier, Jean-Baptiste, Cuniasse, Philippe, Zinn-Justin, Sophie, Marcand, Stéphane, Park, Keunchil, Özgüroğlu, Mustafa, Vansteenkiste, Johan, Spigel, David, Yang, James C.H., Ishii, Hidenobu, Garassino, Marina, de Marinis, Filippo, Szczesna, Aleksandra, Polychronis, Andreas, Uslu, Ruchan, Krzakowski, Maciej, Lee, Jong-Seok, Calabrò, Luana, Arén Frontera, Osvaldo, Xiong, Huiling, Bajars, Marcis, Ruisi, Mary, Barlesi, Fabrice |
| المساهمون: | Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement IRD : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Istanbul University Cerrahpasa, Department of Pulmonology, University Hospitals Leuven Leuven, Sarah Cannon Research Institute Nashville, Tennessee, National Taiwan University Cancer Center Taipei, IRCCS Istituto Nazionale dei Tumori Milano, Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Seoul National University Bundang Hospital (SNUBH), Azienda Ospedaliera Universitaria Senese, EMD Serono Research & Development Institute, Institut Gustave Roussy (IGR), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 1556-0864. |
| بيانات النشر: | HAL CCSD Lippincott, Williams & Wilkins |
| سنة النشر: | 2021 |
| المجموعة: | HAL-CEA (Commissariat à l'énergie atomique et aux énergies alternatives) |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Abstract Specific proteins present at telomeres ensure chromosome end stability, in large part through unknown mechanisms. In this work, we address how the Saccharomyces cerevisiae ORC-related Rif2 protein protects telomere. We show that the small N-terminal Rif2 BAT motif ( B locks A ddition of T elomeres) previously known to limit telomere elongation and Tel1 activity is also sufficient to block NHEJ and 5’ end resection. The BAT motif inhibits the ability of the Mre11-Rad50-Xrs2 complex (MRX) to capture DNA ends. It acts through a direct contact with Rad50 ATP-binding Head domains. Through genetic approaches guided by structural predictions, we identify residues at the surface of Rad50 that are essential for the interaction with Rif2 and its inhibition. Finally, a docking model predicts how BAT binding could specifically destabilise the DNA-bound state of the MRX complex. From these results, we propose that when an MRX complex approaches a telomere, the Rif2 BAT motif binds MRX Head in its ATP-bound resting state. This antagonises MRX transition to its DNA-bound state, and favours a rapid return to the ATP-bound state. Unable to stably capture the telomere end, the MRX complex cannot proceed with the subsequent steps of NHEJ, Tel1-activation and 5’ resection. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03627353; https://amu.hal.science/hal-03627353Test; https://amu.hal.science/hal-03627353/documentTest; https://amu.hal.science/hal-03627353/file/S1556086421018323.pdfTest; PII: S1556-0864(21)01832-3 |
| DOI: | 10.1016/j.jtho.2021.03.009 |
| الإتاحة: | https://doi.org/10.1016/j.jtho.2021.03.009Test https://amu.hal.science/hal-03627353Test https://amu.hal.science/hal-03627353/documentTest https://amu.hal.science/hal-03627353/file/S1556086421018323.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-ncTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.843F25A2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jtho.2021.03.009 |
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