Recruitment of ubiquitin-activating enzyme UBA1 to DNA by poly(ADP-ribose) promotes ATR signalling
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2018-06-21
Date Acceptance
2018-06-14
Citation
Life Science Alliance, 2018, 1 (3), pp.e201800096-e201800096
ISSN
2575-1077
Start Page
e201800096
End Page
e201800096
Journal / Book Title
Life Science Alliance
Volume
1
Issue
3
Copyright Statement
© 2018 Kumbhar et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/)
License URL
Identifier
http://www.life-science-alliance.org/content/1/3/e201800096
Publication Status
Published
Date Publish Online
2018-06-21