Pleiotropic role of PARP1: an overview

Abstract

Poly (ADP-ribose) polymerase 1 (PARP1) protein is encoded by the PARP1 gene located on chromosome 1 (1q42.12) in human cells. It plays a crucial role in post-translational modification by adding poly (ADP-ribose) (PAR) groups to various proteins and PARP1 itself by utilizing nicotinamide adenine dinucleotide (NAD +) as a substrate. Since the discovery of PARP1, its role in DNA repair and cell death has been its identity. This is evident from an overwhelmingly high number of scientific reports in this regard. However, PARP1 also plays critical roles in inflammation, metabolism, tumor development and progression, chromatin modification and transcription, mRNA stability, and alternative splicing. In the present study, we attempted to compile all the scattered scientific information about this molecule, including the structure and multifunctional role of PARP1 in cancer and non-cancer diseases, along with PARP1 inhibitors (PARPis). Furthermore, for the first time, we have classified PARP1-mediated cell death for ease of understanding its role in cell death pathways.

Viewing teratogens through the lens of nicotinamide adenine dinucleotide (NAD+)

“…The nuclear sirtuins (SIRT1, SIRT3 [transiently], SIRT6, and SIRT7), which are dependent on NAD+ as a substrate, regulate DNA damage repair through these pathways, in addition to maintaining telomere length (Lagunas‐Rangel, 2019; Mei et al, 2016). In addition, PARP1, also NAD+ dependent, is involved in the regulation of major DNA repair pathways, such as BER, NER, MMR, NHEJ, HR, and in the maintenance of replication fork stability (Kumar, Kumar, Mir, Yadav, & Chauhan, 2022) (Figure 2).…”

“…BER, base‐excision repair; NER, nucleotide‐excision repair; MMR, DNA mismatch repair; HR, homologous recombination; NHEJ, nonhomologous end joining; ss‐, single strand; ds, double strand. Adapted from Kumar et al (2022), Lagunas‐Rangel (2019), Ruszkiewicz, Bürkle, and Mangerich (2022). Created with BioRender.com.…”

“…For the most part, this mechanism concerns the synthesis or translation of one or another variety of RNA . In addition to regulating DNA repair pathways, PARP1 also acts as a transcription factor and transcriptional coactivator by binding to transcription factors (Kumar et al, 2022). SIRT1 and SIRT6 regulate the transcription factors HIF1α, FOXO1, and its co‐activator PGC1α (Mei et al, 2016).…”

Based on the NF-κB signaling pathway to explore the predictive effect of DNA repair gene PARP1 on distant metastasis after Breast cancer surgery

“…[40]. Research [41] have demonstrated that the in ammatory factor TNF-α, which in turn can activate the PARP1 gene and TNF-α can directly activate the NF-κB pathway, can be expressed by PARP1 and maintain the long-term activation of p65 in the NF-κB pathway. Moreover, research on gastric cancer has demonstrated that PARP1 can control tumor growth via the NF-κB pathway.…”

Biological function, mediate cell death pathway and their potential regulated mechanisms for post-mortem muscle tenderization of PARP1: A review

“…Poly ADP-ribose polymerase 1 is a DNA repair enzyme that has been implicated in DNA damage repair, apoptosis, necrosis, chromosome modification, and transcription ( 7 ). It can interact with Calpain and Caspase to catalyze the degradation of myogenic fibronectin, which in turn regulates muscle tenderness.…”