Scientific Reports - Parp1 deletion rescues cerebellar hypotrophy in xrcc1 mutant zebrafish

Poly (ADP-ribose) Polymerase 1 (PARP1) is an abundant nuclear enzyme that dynamically engages chromatin in diverse cellular scenarios. In the context of DNA repair, PARP1 becomes enzymatically activat...

The tumour-suppressor protein BRCA2 is discovered to have a previously undescribed role in maintaining genomic integrity and the sensitivity of PARP1 inhibitors.

Upon ATR inhibition, APOBEC3B targets unprotected single-stranded DNA at replication forks, leading to fork breakage.

Schützenhofer et al. show that expression of catalytically impaired PARP1 mutants is toxic to cells, which can be overcome by treatment with saruparib, a PARP1-specific inhibitor that displays a pro-r...

RNF114 is an E3 ligase that can recognize ADP-ribose (ADPr) and ubiquitin with separate domains. Using these domains, Kolvenbach and Palumbieri et al. developed a proteomics approach to map ADP-ribosy...

Sorbitol-induced hyperosmotic stress rapidly induces reversible mono(ADP-ribosyl)ation (MARylation) on PARP1 without the signs of genotoxic signaling. We show that PARP1 autoMARylation is HPF1 depend...

PARP inhibitors induce the degradation of an oncogenic YAP1 complex in breast cancer.

Molecular biology; Cell biology; Omics

Hoslett et al. show that trapped PARP1 is cleared from the nucleus by nucleophagy involving the autophagy receptor TEX264 and p97. Inactivation of nucleophagy resensitizes acquired resistance of BRCA1...

Maintaining genomic integrity is essential for the survival of organisms. Here, the authors identify FTO as an endogenous negative regulator of PARP1 and the DNA damage response in cells beyond its ro...

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxicity in homologous recombination repair (HR)-deficient (HRD) cancers by trapping PARP1 on chromatin, thereby causing irreparable replication-associated DNA damage. Although increased clearance of trapped PARP1 from chromatin reduces the sensitivity of cancer cells to PARPi, details surrounding this process remain unclear. PARPi exposure is known to cause increased autophagy flux, whereas autophagy inhibition can hypersensitize cells to PARPi. Our study reveals that trapped PARP1 is cleared via nucleophagy, with the selective autophagy receptor TEX264 and its partner segregase p97 (also known as VCP) orchestrating this process. TEX264 interacts directly with trapped PARP1, linking it to the autophagosomal protein LC3 for degradation. Disrupting this pathway, either chemically or genetically, increases PARP1 trapping, resulting in protein aggregates, DNA damage and cell lethality, ultimately re-sensitizing PARPi-resista

(Cell Reports 45, 117350; May 26, 2026)

Poly(ADP-ribose) polymerase 1 (PARP1) is established as a key regulator of the cellular DNA damage response and apoptosis. In addition, PARP1 participates in...

ATR is the master safeguard of genomic integrity during DNA replication. Acute inhibition of ATR with ATR inhibitor (ATRi) triggers a surge in origin firing, leading to increased levels of single-stra...

Abstract. Although poly-(ADP ribose) polymerase 1 (PARP1) and PARylation of histones have been known for over 50 years and have been successfully targeted

El doctor en medicina por la Universidad de Harvard se muestra confiado en tratamientos como la metformina o los inhibidores de PARP1. Hasta que estos se aprueben, practica el ayuno intermitente

Poly(ADP-ribose) polymerase1 (PARP1) plays a vital role in DNA repair and its inhibition in cancer cells may cause cell apoptosis. In this study, we investigated the effects of a PARP1 variant, V762A,...

Poly(ADP-ribose) polymerase1 (PARP1) plays a vital role in DNA repair, and its inhibition in cancer cells may cause cell apoptosis. In this study, we investigated the effects of a PARP1 variant, V762A, which is strongly associated with several cancers in humans, on the inhibition of PARP1 by three FDA-approved inhibitors: niraparib, rucaparib, and talazoparib. Specifically, we compared the inhibition of the mutant to that of wild-type (WT) PARP1. Additionally, we investigated how the mutation influences the binding of these inhibitors to PARP1. Our work suggests that while mutant PARP1 exhibits only minor differences in residual fluctuations, backbone deviations, and residue motion correlations compared to the WT under niraparib and rucaparib inhibitions, it shows significant and distinct differences in these features when inhibited by talazoparib. Among the three inhibitions, talazoparib inhibition uniquely lowers the average residue fluctuations in the mutant than the WT including lower fluctuations of mutant’s N- and C-terminal residues in the catalytic domain, conserved H-Y-E traid residues, and donor loop (D-loop) residues which are important for catalysis more effectively than other inhibitions. However, talazoparib also significantly enhances destabilizing interactions between the mutation site in the HD domain in the mutant than WT. Further, among the three inhibitions, talazoparib inhibition uniquely and significantly disrupts the functional fluctuations of terminal regions in the mutant, which are otherwise present in the WT. The mutation and inhibition do not significantly affect PARP1’s essential dynamics. Lastly, these inhibitors bind to the V762A mutant more effectively than to the WT, with similar binding free energies between them.