PreprintArticleVersion 1This version is not peer-reviewed
Biologically Relevant Polyamines, Divalent Metal Cations, and Structure of Poly(ADP-Ribose) All Control Microphase Separation of FUS with Poly(ADP-Ribosyl)ated PARP1
Version 1
: Received: 30 September 2024 / Approved: 1 October 2024 / Online: 3 October 2024 (07:55:14 CEST)
How to cite:
Sukhanova, M. V.; Anarbaev, R. O.; Naumenko, K. N.; Hamon, L.; Singatulina, A. S.; Pastre, D.; Lavrik, O. I. Biologically Relevant Polyamines, Divalent Metal Cations, and Structure of Poly(ADP-Ribose) All Control Microphase Separation of FUS with Poly(ADP-Ribosyl)ated PARP1. Preprints2024, 2024100023. https://doi.org/10.20944/preprints202410.0023.v1
Sukhanova, M. V.; Anarbaev, R. O.; Naumenko, K. N.; Hamon, L.; Singatulina, A. S.; Pastre, D.; Lavrik, O. I. Biologically Relevant Polyamines, Divalent Metal Cations, and Structure of Poly(ADP-Ribose) All Control Microphase Separation of FUS with Poly(ADP-Ribosyl)ated PARP1. Preprints 2024, 2024100023. https://doi.org/10.20944/preprints202410.0023.v1
Sukhanova, M. V.; Anarbaev, R. O.; Naumenko, K. N.; Hamon, L.; Singatulina, A. S.; Pastre, D.; Lavrik, O. I. Biologically Relevant Polyamines, Divalent Metal Cations, and Structure of Poly(ADP-Ribose) All Control Microphase Separation of FUS with Poly(ADP-Ribosyl)ated PARP1. Preprints2024, 2024100023. https://doi.org/10.20944/preprints202410.0023.v1
APA Style
Sukhanova, M. V., Anarbaev, R. O., Naumenko, K. N., Hamon, L., Singatulina, A. S., Pastre, D., & Lavrik, O. I. (2024). Biologically Relevant Polyamines, Divalent Metal Cations, and Structure of Poly(ADP-Ribose) All Control Microphase Separation of FUS with Poly(ADP-Ribosyl)ated PARP1. Preprints. https://doi.org/10.20944/preprints202410.0023.v1
Chicago/Turabian Style
Sukhanova, M. V., David Pastre and Olga I Lavrik. 2024 "Biologically Relevant Polyamines, Divalent Metal Cations, and Structure of Poly(ADP-Ribose) All Control Microphase Separation of FUS with Poly(ADP-Ribosyl)ated PARP1" Preprints. https://doi.org/10.20944/preprints202410.0023.v1
Abstract
Fused in sarcoma (FUS) is involved in the formation of nuclear biomolecular condensates associated with poly(ADP-ribose) [PAR] synthesis catalyzed by a DNA damage sensor such as PARP1. Here, we studied FUS microphases’ separation induced by poly(ADP-ribosyl)ated PARP1WT [PAR-PARP1WT] or its mutants PARP1Y986S and PARP1Y986H respectively synthesizing (short PAR)-PARP1Y986S or (short hyperbranched PAR)-PARP1Y986H using dynamic light scattering, fluorescence microscopy, turbidity assays, and atomic force microscopy. We observed that biologically relevant cations such as Mg2+, Ca2+, or Mn2+ or polyamines (spermine4+ or spermidine3+) were essential for the assembly of FUS with PAR-PARP1WT and FUS with PAR-PARP1Y986S in vitro. We estimated the range of the FUS-to-PAR-PARP1 molar ratio and the cation concentration that are favorable for the stability of the protein’s microphase-separated state. We also found that FUS microphase separation induced by PAR-PARP1Y986H (i.e., a PARP1 mutant attaching short hyperbranched PAR to itself) can occur in the absence of cations. The dependence of PAR-PARP1–induced FUS microphase separation on cations and on branching of PAR structure points to a potential role of the latter in the regulation of formation of FUS-related biological condensates and requires further investigation.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
