RT Journal Article
SR Electronic
T1 Recruitment of ubiquitin-activating enzyme UBA1 to DNA by poly(ADP-ribose) promotes ATR signalling
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800096
DO 10.26508/lsa.201800096
VO 1
IS 3
A1 Ramhari Kumbhar
A1 Sophie Vidal-Eychenié
A1 Dimitrios-Georgios Kontopoulos
A1 Marion Larroque
A1 Christian Larroque
A1 Jihane Basbous
A1 Sofia Kossida
A1 Cyril Ribeyre
A1 Angelos Constantinou
YR 2018
UL https://www.life-science-alliance.org/content/1/3/e201800096.abstract
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.