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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Added by pmartino
Group name EquipePM
Item Type Journal Article
Title Recruitment of ubiquitin-activating enzyme UBA1 to DNA by poly(ADP-ribose) promotes ATR signalling
Creator Kumbhar et al.
Author Ramhari Kumbhar
Author Sophie Vidal-Eychenié
Author Dimitrios-Georgios Kontopoulos
Author Marion Larroque
Author Christian Larroque
Author Jihane Basbous
Author Sofia Kossida
Author Cyril Ribeyre
Author Angelos Constantinou
Abstract The DNA damage response (DDR) ensures cellular adaptation to genotoxic insults. In the crowded environment of the nucleus, the assembly of productive DDR complexes requires multiple protein modifications. How the apical E1 ubiquitin activation enzyme UBA1 integrates spatially and temporally in the DDR remains elusive. Using a human cell-free system, we show that poly(ADP-ribose) polymerase 1 promotes the recruitment of UBA1 to DNA. We find that the association of UBA1 with poly(ADP-ribosyl)ated protein-DNA complexes is necessary for the phosphorylation replication protein A and checkpoint kinase 1 by the serine/threonine protein kinase ataxia-telangiectasia and RAD3-related, a prototypal response to DNA damage. UBA1 interacts directly with poly(ADP-ribose) via a solvent-accessible and positively charged patch conserved in the Animalia kingdom but not in Fungi. Thus, ubiquitin activation can anchor to poly(ADP-ribose)-seeded protein assemblies, ensuring the formation of functional ataxia-telangiectasia mutated and RAD3-related-signalling complexes.
Publication Life Science Alliance
Volume 1
Issue 3
Pages e201800096
Date Jun 2018
Journal Abbr Life Sci Alliance
Language eng
DOI 10.26508/lsa.201800096
ISSN 2575-1077
Library Catalog PubMed
Extra PMID: 30456359 PMCID: PMC6238597
Tags arc, epigenmed, original, private, siric
Date Added 2018/11/29 - 10:55:50
Date Modified 2021/03/05 - 10:43:56
Notes and Attachments PubMed entry (Attachment)
Texte intégral (Attachment)


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