Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). / Altmeyer, Matthias; Neelsen, Kai J; Teloni, Federico; Pozdnyakova, Irina; Pellegrino, Stefania; Grøfte, Merete; Rask, Maj-Britt Druedahl; Streicher, Werner; Jungmichel, Stephanie; Nielsen, Michael Lund; Lukas, Jiri.

In: Nature Communications, Vol. 6, 8088, 19.08.2015, p. 1-12.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Altmeyer, M, Neelsen, KJ, Teloni, F, Pozdnyakova, I, Pellegrino, S, Grøfte, M, Rask, M-BD, Streicher, W, Jungmichel, S, Nielsen, ML & Lukas, J 2015, 'Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)', Nature Communications, vol. 6, 8088, pp. 1-12. https://doi.org/10.1038/ncomms9088

APA

Altmeyer, M., Neelsen, K. J., Teloni, F., Pozdnyakova, I., Pellegrino, S., Grøfte, M., ... Lukas, J. (2015). Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). Nature Communications, 6, 1-12. [8088]. https://doi.org/10.1038/ncomms9088

Vancouver

Altmeyer M, Neelsen KJ, Teloni F, Pozdnyakova I, Pellegrino S, Grøfte M et al. Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). Nature Communications. 2015 Aug 19;6:1-12. 8088. https://doi.org/10.1038/ncomms9088

Author

Altmeyer, Matthias ; Neelsen, Kai J ; Teloni, Federico ; Pozdnyakova, Irina ; Pellegrino, Stefania ; Grøfte, Merete ; Rask, Maj-Britt Druedahl ; Streicher, Werner ; Jungmichel, Stephanie ; Nielsen, Michael Lund ; Lukas, Jiri. / Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). In: Nature Communications. 2015 ; Vol. 6. pp. 1-12.

Bibtex

@article{c67d2b9900a04649ad0b7bb616910b6f,
title = "Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)",
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 charged RGG repeats and negatively charged PAR, is amplified by aggregation-prone prion-like domains, and orchestrates the earliest cellular responses to DNA breakage. We propose that PAR-seeded liquid demixing is a general mechanism to dynamically reorganize the soluble nuclear space with implications for pathological protein aggregation caused by derailed phase separation.",
author = "Matthias Altmeyer and Neelsen, {Kai J} and Federico Teloni and Irina Pozdnyakova and Stefania Pellegrino and Merete Gr{\o}fte and Rask, {Maj-Britt Druedahl} and Werner Streicher and Stephanie Jungmichel and Nielsen, {Michael Lund} and Jiri Lukas",
year = "2015",
month = "8",
day = "19",
doi = "10.1038/ncomms9088",
language = "English",
volume = "6",
pages = "1--12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)

AU - Altmeyer, Matthias

AU - Neelsen, Kai J

AU - Teloni, Federico

AU - Pozdnyakova, Irina

AU - Pellegrino, Stefania

AU - Grøfte, Merete

AU - Rask, Maj-Britt Druedahl

AU - Streicher, Werner

AU - Jungmichel, Stephanie

AU - Nielsen, Michael Lund

AU - Lukas, Jiri

PY - 2015/8/19

Y1 - 2015/8/19

N2 - 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 charged RGG repeats and negatively charged PAR, is amplified by aggregation-prone prion-like domains, and orchestrates the earliest cellular responses to DNA breakage. We propose that PAR-seeded liquid demixing is a general mechanism to dynamically reorganize the soluble nuclear space with implications for pathological protein aggregation caused by derailed phase separation.

AB - 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 charged RGG repeats and negatively charged PAR, is amplified by aggregation-prone prion-like domains, and orchestrates the earliest cellular responses to DNA breakage. We propose that PAR-seeded liquid demixing is a general mechanism to dynamically reorganize the soluble nuclear space with implications for pathological protein aggregation caused by derailed phase separation.

U2 - 10.1038/ncomms9088

DO - 10.1038/ncomms9088

M3 - Journal article

C2 - 26286827

VL - 6

SP - 1

EP - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 8088

ER -

ID: 142913000