Ask about this productRelated genes to: PARP2 antibody
- Gene:
- PARP2 NIH gene
- Name:
- poly(ADP-ribose) polymerase 2
- Previous symbol:
- ADPRTL2
- Synonyms:
- -
- Chromosome:
- 14q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-24
- Date modifiied:
- 2015-11-06
Related products to: PARP2 antibody
Related articles to: PARP2 antibody
- Pancreatic cancer represents one of the most lethal tumors, characterized by an immunosuppressive microenvironment and a lack of cytotoxic immune cell infiltrates, which confer resistance to immunotherapy. Here, we demonstrate that deletion of poly(ADP-ribose) polymerase 2 (PARP2) in a -driven mouse model of pancreatic cancer delays tumor progression and increases survival. Mechanistically, PARP2 loss induces enrichment of pathways associated with genomic instability and replicative stress, leading to increased γH2AX, chromosomal instability, and micronuclei accumulation. In addition to these tumor-intrinsic effects, PARP2 deletion reshapes the tumor microenvironment, promoting infiltration of cytotoxic T and natural killer cells while reducing immunosuppressive cell populations, enhancing antitumor cytotoxicity. These findings are recapitulated in a -driven orthotopic pancreatic ductal adenocarcinoma model. Collectively, our data support selective PARP2 inhibition as a promising therapeutic strategy for pancreatic cancer by impairing genome integrity and boosting antitumor immune response, thereby opening potential avenues for combating this devastating disease. - Source: PubMed
Publication date: 2026/05/08
Martínez-Bosch NeusManero-Rupérez NoemíVázquez-Bellón NúriaNickell-Hernández BennettVentura-Blanch CristinaLutfi NuraLechuga Carmen GMartínez CarlosMoreno MireiaAmpurdanés CoralAbad EtnaIglesias MarMuñoz-Escribano MaríaJanic AnaRovira MeritxellGuerra CarmenRabinovich Gabriel AYélamos JoséNavarro Pilar - The successful use of PARP inhibitors against primarily homologous recombination-deficient tumors relies on their ability to inhibit the catalytic activity of PARP1 and PARP2, leading to their retention at sites of DNA damage, known as PARP "trapping." Different PARP inhibitors vary in their trapping ability and thus in their resulting toxicity. Here, we develop an inducible complementation system for the expression of tagged PARP1 variants to assess the impact of different mutations in the PARP1 catalytic site on ADP-ribosylation (ADPr) activity, trapping, and cell survival. Testing these cell lines for their behavior and sensitivity to different PARP inhibitors, we find that saruparib, a first-in-class PARP1-specific inhibitor, promotes the release of certain PARP1 catalytic mutants and resistance to this inhibitor. We also characterize a PARP1 catalytic mutant with intact mono(ADP-ribosyl)ation activity but devoid of poly(ADP-ribosyl)ation, enabling us to demonstrate a significant contribution of mono(ADP-ribosyl)ation toward PARP1 release from sites of DNA damage. - Source: PubMed
Publication date: 2026/05/04
Schützenhofer KiraLaker EllenTsang KyleBaretić DomagojSuskiewicz Marcin JZobel Florian F HSimmons Michael D RChatrin ChatrinSmith RebeccaAhel Ivan - Poly(ADP-ribose) (PAR) is a polymer of ADP-ribose synthesized by four members of the ADP-ribose polymerase family of enzymes-PARP1, PARP2, PARP5a, and PARP5b. However, only PARP1 and PARP2 synthesize PAR in response to DNA breaks. PAR is defined as a protein post-translational modification, but it is also shown to exist as a DNA or RNA modification. Levels of PAR are further regulated by PARG, a PAR glycohydrolase that, together with PARP1 and PARP2, modulates the cellular level of DNA damage-induced PAR. The dynamic synthesis and degradation of PAR is critical to its regulatory role in DNA repair, and the DNA damage response, which in turn affects chromatin reorganization, replication, transcription, and cell death. PARP1/PARP2 activation and the accumulation of PAR can be considered sites of ongoing base excision repair or DNA single-strand break repair; however, numerous PARP1/PARP2 activators are also associated with replication stress and other DNA metabolic processes. Once formed, PAR chains facilitate the recruitment of DNA repair and DNA damage response (DDR) factors to sites of DNA damage or genomic insult via their PAR-binding domains (PBDs). Ten different PBDs recognize various regions of the PAR molecule, including the PAR binding motif, PAR binding Zinc finger, the WWE domain, and the macrodomain, among other PBDs. To facilitate cellular analysis of PAR dynamics, we used PBDs fused to enhanced green fluorescent protein (EGFP) to optimize cell-based quantitation of PAR foci. We describe an assay that uses a fragment of RNF146 encoding the PBD/WWE domain, linked to EGFP, to visualize and quantify PAR accumulation at sites of genomic insult and ongoing BER or SSBR. We describe experimental steps, including the production of lentiviral particles, transduction of the target cell line, treatment of mammalian cells to induce genomic DNA damage, acquisition of confocal fluorescence micrographs, and semi-automated quantification of the data. - Source: PubMed
Publication date: 2026/04/17
Roos Wynand PAl-Rahahleh Rasha QKoczor Christopher ABeers Libby ABoyang LouisSobol Robert W - Accurate prediction of inhibitor selectivity across protein paralogues remains a central challenge in computational drug discovery. Here, we perform a comparative assessment of three computational methods─Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA), Absolute Binding Free Energy (ABFE) and Umbrella Sampling (US) calculations─in their ability to recapitulate PARP1 versus PARP2 selectivity for eight clinically relevant PARP enzyme inhibitors used in ovarian, breast, and prostate tumors, among others. We demonstrate how MM/PBSA calculations offer rapid and qualitative insights but show pronounced sensitivity to the chosen static conformational pose, being particularly challenging for ligands with subtle energetic differences between distinct protein paralogues. In contrast, both ABFE and US calculations using atomistic models with explicit solvent result in substantially improved agreement with experimental binding affinities. The ABFE method exhibits the strongest quantitative correlation with experimental binding free energy differences, remarkably reproducing selectivity trends even among nearly isoenergetic complexes. Notably, our structural contact analysis reveals how contact connectivity controls ligand selectivity, providing valuable mechanistic and molecular insight into the key residues that stabilize each inhibitor in both protein enzymes. Together, our multimethod computational study contributes to elucidating potential chemical modifications across the ligand chemical space to enhance potency and specificity, informing the future design and evaluation of selective inhibitors for precision oncology, including therapies targeting homologous recombination-deficient cancers. - Source: PubMed
Publication date: 2026/04/18
Feito AlejandroDeMoya-Valenzuela NatàliaPrivat CristianTejedor Andrés RDelValle-Carrillo MarcoCembellín SaraPaniagua-Herranz LucíaGaraizar AdiranOller-Iscar JavierOcana AlbertoEspinosa Jorge R - Poly(ADP-ribose) polymerase 2 (PARP2) is a key sensor of DNA single-strand breaks that catalyzes ADP-ribosylation of itself and other substrates to initiate DNA repair. Human PARP2 contains an intrinsically disordered N-terminal domain (NTD) that mediates chromatin association and nuclear localization, a central WGR domain that recognizes DNA breaks, and a catalytic domain responsible for poly(ADP-ribose) synthesis. Despite its importance in genome maintenance and as a target of clinical PARP inhibitors, detailed information on the structural and dynamic properties of the NTD and WGR domains has remained limited. Here, we report the H, C, and N resonance assignments of the N-terminal intrinsically disordered region (residues 1–89) and the WGR domain (residues 90–212) of human PARP2. Resonance assignments were first obtained separately for each domain and subsequently transferred to a combined NTD–WGR construct. These assignments provide a foundation for future studies investigating the conformational dynamics, DNA recognition mechanisms, and allosteric regulation of PARP2 in chromatin and repair signaling. - Source: PubMed
Publication date: 2026/04/09
Virk Rajbinder KKim Tae Hun