Poly(ADP-ribosyl)ation temporally confines SUMO-dependent ataxin-3 recruitment to control DNA double-strand break repair
- 1 February 2021
- journal article
- research article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 134 (3)
- https://doi.org/10.1242/jcs.247809
Abstract
DNA damage-induced SUMOylation serves as a signal for two antagonizing proteins that both stimulate repair of DNA double strand breaks (DSBs). Here, we demonstrate that the SUMO-dependent recruitment of the deubiquitylating enzyme ataxin-3 to DSBs, unlike recruitment of the ubiquitin ligase RNF4, additionally depends on PARP1-mediated poly(ADP-ribosyl)ation (PARylation). The co-dependence of ataxin-3 recruitment on PARylation and SUMOylation temporally confines its presence at DSBs to a short time window directly following detection of the DNA damage. We propose that this mechanism ensures that ataxin-3 prevents the premature removal of DNA repair proteins only during the early phase of the DSB response and does not interfere with the subsequent timely displacement of DNA repair proteins by RNF4. Thus, our data show that PARylation differentially regulates SUMO-dependent recruitment of ataxin-3 and RNF4 to DSBs, explaining how both proteins can play a stimulatory role at DSBs despite their opposing activities.Keywords
Funding Information
- Vetenskapsrådet (2016-02479)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (016.161.32)
- Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-05868, RGPAS-492875-2016)
- European Research Council (ERC-CoG 617485)
- Cancerfonden (CAN2018/693)
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