Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)
University of Copenhagen · University of Zurich · +1 more institution
Abstract
Abstract Intrinsically disordered proteins can phase separate from the soluble intracellular space, and tend to aggregate under pathological conditions. The physiological functions and molecular triggers of liquid demixing by phase separation are not well understood. Here we show in vitro and in vivo that the nucleic acid-mimicking biopolymer poly(ADP-ribose) (PAR) nucleates intracellular liquid demixing. PAR levels are markedly induced at sites of DNA damage, and we provide evidence that PAR-seeded liquid demixing results in rapid, yet transient and fully reversible assembly of various intrinsically disordered proteins at DNA break sites. Demixing, which relies on electrostatic interactions between positively…
Citation impact
- FWCI
- 18.18
- Percentile
- 100%
- References
- 51
Authors
11- MAMatthias AltmeyerCorresponding
University of Copenhagen, University of Zurich, Novo Nordisk Foundation
- KJKai J. Neelsen
University of Copenhagen, Novo Nordisk Foundation
- FTFederico Teloni
University of Zurich
- IPIrina Pozdnyakova
University of Copenhagen, Novo Nordisk Foundation
- SPStefania Pellegrino
University of Zurich
Topics & keywords
- Intrinsically disordered proteins
- Ribose
- Seeding
- Chemistry
- Biophysics
- Biochemistry
- Cell biology
- Biology