PT  - JOURNAL ARTICLE
AU  - Ramhari Kumbhar
AU  - Sophie Vidal-Eychenié
AU  - Dimitrios-Georgios Kontopoulos
AU  - Marion Larroque
AU  - Christian Larroque
AU  - Jihane Basbous
AU  - Sofia Kossida
AU  - Cyril Ribeyre
AU  - Angelos Constantinou
TI  - Recruitment of ubiquitin-activating enzyme UBA1 to DNA by poly(ADP-ribose) promotes ATR signalling
AID  - 10.26508/lsa.201800096
DP  - 2018 Jun 01
TA  - Life Science Alliance
PG  - e201800096
VI  - 1
IP  - 3
4099  - https://www.life-science-alliance.org/content/1/3/e201800096.short
4100  - https://www.life-science-alliance.org/content/1/3/e201800096.full
SO  - Life Sci. Alliance2018 Jun 01; 1
AB  - 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.