2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
September 1st, 2025
Version: 1
Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia
molecular biology
bioRxiv

HPF1 REGULATES THE FORMATION OF FUS-DEPENDENT COMPARTMENTS BY PARP1 AND PARP2 ACTIVATION ON DAMAGED DNA

Singatulina, A. S.Open in Google Scholar•Sukhanova, M. V.Open in Google Scholar•Hamon, L.Open in Google Scholar•Kutuzov, M. M.Open in Google Scholar•Pastre, D.Open in Google Scholar•Lavrik, O.Open in Google Scholar

FUS participates in the formation of biomolecular condensates associated with PARP1-dependent synthesis of poly(ADP-ribose) (PAR). HPF1 regulates auto- and hetero-PARylation activities of PARP1 and PARP2 and may influence the formation of FUS compartments during PARP1 or PARP2 auto-PARylation. In this study, we used atomic force microscopy in combination with biochemical assay to investigate the formation of FUS compartments under activation of PARP1 and PARP2, when HPF1 modulates their activity. Similar to PARP1, FUS and PARylated PARP2 form DNA-rich compartments, indicating that PARP2 PARylation is sufficient for the formation of such compartments. The excess of HPF1 over PARP1 diminishes PARP1 activity and reduces the size of DNA-rich compartments. However, an excess of HPF1 over PARP2 does not significantly affect PARP2 activity and the size of compartments. Furthermore, HPF1 stimulates hetero-PARylation of FUS; this modification is stronger with PARP2 than with PARP1. HPF1-dependent intensive PARylation of FUS catalyzed by PARP1 or PARP2 impairs the assembly of DNA-rich compartment. These data provide a basis for investigating the effect of HPF1 on the formation of PAR-dependent condensates involving RNA-binding proteins like FUS, which interact effectively with PAR and show the ability to be targets of PARylation to regulate condensate formation at DNA damage sites

Similar Papers

bioRxiv
Wed Sep 03 2025
Pmt1-dependent and state-restricted DNA methylation in fission yeast
DNA 5-methylcytosine (5mC) is widely considered absent from budding and fission yeasts. The Dnmt2 family enzyme Pmt1 in Schizosaccharomyces pombe is annotated as a tRNA C38 methyltransferase, but whether it methylates DNA in vivo has remained unresolved. Using orthogonal chemistry (HPLC/LC-MS and 1H-NMR) with external standards (limit of detection for 5mdC = 0.0125 mM), we detect authentic 5-methy...
MILED, S.
bioRxiv
Wed Sep 03 2025
Impaired Lung BCAA Metabolism Promotes Ferroptosis and Resultant Pulmonary Arterial Hypertension-Associated Hepatopathy
Background: Dysregulated branched chain amino acid (BCAA) homeostasis occurs in pulmonary arterial hypertension (PAH) as BCAA metabolites accumulate and cause metabolic alterations in pulmonary artery smooth muscle cells (PASMC). In other cells, altered BCAA metabolism promotes ferroptosis, a PAH-inducing metabolic pathway. However, the interplay between BCAAs, lung ferroptosis, and PAH is unexplo...
Blake, M.
•
Hong, J.
•
Brownstein, A.
•
Rhodes, C.
...•
Prins, K.
bioRxiv
Wed Sep 03 2025
Evaluation of nanopore sequencing for increasing accessibility of eDNA studies in biodiverse countries
Biodiversity loss is a global challenge of the 21st century. Environmental DNA (eDNA)-based metabarcoding offers a cost- and time-efficient alternative to conventional biodiversity surveys, enabling detection of rare, cryptic, and elusive species from environmental samples. However, limited access to genomic technologies restricts the application of eDNA metabarcoding in highly biodiverse remote r...
Gygax, D.
•
Ramirez, S.
•
Chibesa, M.
•
Simpamba, T.
...•
Zulu, G.
bioRxiv
Wed Sep 03 2025
The Glc7/PP1 phosphatase triggers Paf1C dissociation from RNA polymerase II to enable transcription termination
The mechanisms that control the dynamic composition of RNAPII elongation complexes govern major transitions in the transcription cycle yet are poorly understood. Here, we show that the transcription elongation factor Spt5 determines elongation complex composition to promote productive elongation and the transition to termination. Using an unbiased genetic screen and genomic approaches in Saccharom...
Namjilsuren, S.
•
Arndt, K. M.
bioRxiv
Wed Sep 03 2025
Recurrent DNA Break Clusters Regulated by Polymerase Theta Are Essential for Replication Stress Induced Copy Number Variation
Copy number variations (CNVs) are a form of genetic alteration strongly implicated in numerous neurological and psychiatric disorders, as well as brain cancer. Replication stress is a common cause of CNVs. Despite the prevailing model that CNVs arise from DNA double strand breaks (DSBs), there has been no assay that directly perturbs presumed DSB sources and measures CNV output. Here, we identifie...
Corazzi, L.
•
Ing, A.
•
Ionasz, V.
•
Marx, A.
...•
Wei, P.-C.
bioRxiv
Tue Sep 02 2025
Mapping early PRC2 nucleation sites upon Suz12 reintroduction reveals features of de novo Polycomb recruitment
Polycomb domains safeguard cell identity by maintaining lineage-specific chromatin states enriched in repressive histone modifications, preserving the epigenetic memory of cell lineages. While Polycomb Repressive Complex 2 (PRC2) can re-establish its occupancy after perturbation, the mechanisms that guide de novo Polycomb recruitment remain unclear. To address this, we engineered an auxin-inducibl...
Hernandez-Romero, I. A.
•
Peralta-Alvarez, C. A.
•
Roman-Figueroa, A.
•
Cano-Dominguez, N.
...•
Valdes, J.
bioRxiv
Tue Sep 02 2025
A compendium of bona fide reference markers for genuine plant-derived extracellular vesicles and their degree of phylogenetic conservation
Although the field of plant EVs (PEVs) is experiencing exponential growth, rigorous characterisation complying with MISEV guidelines has not been yet implemented due to the lack of bona fide reference markers. In this work, we have paved the way for the standardisation of PEV markers, providing the most profound proteomic data so far from apoplastic washing fluid-EVs, a sample enriched in genuine ...
Rodriguez de Lope, M. M.
•
Sanchez-Pajares, I. R.
•
Herranz, E.
•
Lopez-Vazquez, C. M.
...•
de la Cuesta, F.
bioRxiv
Tue Sep 02 2025
Differential quantitative requirements for pre-mRNA splicing-regulated shelterin protein levels in distinct telomere functions
Telomeres perform multiple functions to maintain genome stability, including telomere length regulation, chromosome end protection, and meiotic chromosome dynamics. These functions are governed by shelterin, a telomere-binding protein complex. Here, we show that efficient pre-mRNA splicing of the Schizosaccharomyces pombe shelterin components Rap1 and Poz1 ensures sufficient protein levels, which ...
Takeuchi, M.
•
Otsubo, Y.
•
Kanoh, J.
bioRxiv
Tue Sep 02 2025
PXDesign: Fast, Modular, and Accurate De Novo Design of Protein Binders
PXDesign achieves nanomolar binder hit rates of 20-73% across five of six diverse protein targets, surpassing prior methods such as AlphaProteo. This experimental success rate is enabled by advances in both binder generation and filtering. We develop both a diffusion-based generative model (PXDesign-d) and a hallucination-based approach (PXDesign-h), each showing strong in silico performance that ...
Ren, M.
•
Sun, J.
•
Guan, J.
•
Liu, C.
...•
Xiao, W.
bioRxiv
Mon Sep 01 2025
Reliable Detection of SGLT2 Protein through Knockout-based Antibody Characterization and Optimized Procedures
Introduction: Sodium-glucose cotransporter 2 (SGLT2) is a key mediator of renal glucose reabsorption. Its pharmacological inhibition exerts cardiac- and reno-protective benefits. Despite widespread clinical interest, reliable detection of SGLT2 protein remains challenging due to concerns regarding the specificity of available antibodies. Methods: This study assessed the specificity of eight commer...
Hirose, T.
•
Ito, H.
•
Endo, A.
•
Sato, S.
...•
Mori, T.