PARprolink: a photoaffinity probe for identifying poly(ADP-ribose)-binding proteins
Dasovich, M.; Beckett, M. Q.; Bailey, S.; Ong, S.-E.; Greenberg, M.; Leung, A.
Show abstract
Post-translational modification of proteins with poly(ADP-ribose) (PAR) is an important component of the DNA damage response. Four PAR synthesis inhibitors have recently been approved for the treatment of breast, ovarian, and prostate cancers. Despite its clinical significance, a molecular understanding of PAR function, including its binding partners, remains incomplete. In this work, we synthesize a PAR photoaffinity probe that captures and isolates endogenous PAR binders. Our method identified dozens of known PAR-binding proteins and hundreds of novel binders involved in DNA repair, RNA processing, and metabolism. PAR binding by eight candidates was confirmed using pull-down and/or electrophoretic mobility shift assays. Using PAR probes of defined lengths, we detected proteins that preferentially bind to 40-mer over 8-mer PAR, indicating that polymer length may regulate the outcome and timing of PAR signaling pathways. This investigation produces the first census of PAR-binding proteins, provides a proteome-wide view of length-selective PAR binding, and associates PAR binding with RNA metabolism and the formation of biomolecular condensates.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- HPF1 dynamically controls the PARP1/2 balance between initiating and elongating ADPribose modifications 95%
- Spatially resolved profiling of protein conformation and interactions by biocompatible chemical cross-linking in living cells 95%
- Visualization of liquid-liquid phase transitions using a tiny G-quadruplex binding protein 94%
Similar papers in this journal
- Cell-Surface RNA Forms Ternary Complex with RNA-Binding Proteins and Heparan Sulfate to Recruit Immune Receptors 94%
- Productive mRNA Chromatin Escape is Promoted by PRMT5 Methylation of SNRPB 93%
- RAPIDASH: A tag-free enrichment of ribosome-associated proteins reveals compositional dynamics in embryonic tissues and stimulated macrophages 93%
Similar papers in this journal
- Spatiotemporal proximity labeling tools to track GlcNAc sugar-modified functional protein hubs during cellular signaling 94%
- Tunable hetero-assembly of a plant pseudoenzyme-enzyme complex 93%
- Multiplex, quantitative, high-resolution imaging of protein:protein complexes via hybridization chain reaction 93%
Similar papers in this journal
- Deep profiling of protease substrate specificity enabled by dual random and scanned human proteome substrate phage libraries 94%
- RNA-protein interaction mapping via MS2 or Cas13-based APEX targeting 93%
- Targeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of Nsp1, Nsp2, and Nucleocapsid proteins from SARS-CoV-2 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.