The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)
Open accessAbstract
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.
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Cites
Systematic identification of genomic markers of drug sensitivity in cancer cells
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Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663
ATM-Dependent Chromatin Changes Silence Transcription In cis to DNA Double-Strand Breaks
Shanbhag, N. M., Rafalska-Metcalf, I. U., Balane-Bolivar, C., Janicki, S. M., & Greenberg, R. A. (2010) · Cell · doi:10.1016/j.cell.2010.04.038 · Cited by 737
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Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins
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A Macrohistone Variant Links Dynamic Chromatin Compaction to BRCA1-Dependent Genome Maintenance
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Lyon, A. S., Peeples, W. B., & Rosen, M. K. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00303-z · Cited by 895
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
Gupte, R., Liu, Z., & Kraus, W. L. (2017) · Genes & Development · doi:10.1101/gad.291518.116 · Cited by 681
“This phase separation, which dynamically reorganizes the soluble nuclear space, orchestrates the earliest cellular responses to DNA damage (Altmeyer et al. 2015).”
BackgroundThe code and beyond: transcription regulation by the RNA polymerase II carboxy-terminal domain
Harlen, K. M., & Churchman, L. S. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.10 · Cited by 499
Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease
Kam, T.-I., Mao, X., Park, H., Chou, S.-C., Karuppagounder, S. S., Umanah, G. E., Yun, S. P., Brahmachari, S., Panicker, N., Chen, R., et al. (2018) · Science · doi:10.1126/science.aat8407 · Cited by 476
Relationship of sequence and phase separation in protein low-complexity regions
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Metadata
- Authors
- Altmeyer, M., Neelsen, K. J., Teloni, F., Pozdnyakova, I., Pellegrino, S., Grøfte, M., Rask, M.-B. D., Streicher, W., Jungmichel, S., Nielsen, M. L., & Lukas, J.
- Venue
- Nature Communications
- Published
- 2015-08-19
- Volume
- 6
- Issue
- 1
- Pages
- 8088-8088
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2271817176
- Cited by
- 587
- References
- 7
- FWCI
- 15.44
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). https://app.cochat.ai/papers/10.1038/ncomms9088
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- Altmeyer, M., Neelsen, K. J., Teloni, F., Pozdnyakova, I., Pellegrino, S., Grøfte, M., Rask, M.-B. D., Streicher, W., Jungmichel, S., Nielsen, M. L., & Lukas, J. (2015). Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). Nature Communications. https://doi.org/10.1038/ncomms9088
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