Poly(ADP-Ribosyl) Code Functions

Abstract

Poly(ADP-ribosyl)ation plays a key role in cellular metabolism. Covalent poly(ADP-ribosyl)ation affects the activity of the proteins engaged in DNA repair, chromatin structure regulation, gene expression, RNA processing, ribosome biogenesis, and protein translation. Non-covalent PAR-dependent interactions are involved in the various types of cellular response to stress and viral infection, such as inflammation, hormonal signaling, and the immune response. The review discusses how structurally different poly(ADP-ribose) (PAR) molecules composed of identical monomers can differentially participate in various cellular processes acting as the so-called PAR code. The article describes the ability of PAR polymers to form functional biomolecular clusters through a phase-separation in response to various signals. This phase-separation contributes to rapid spatial segregation of biochemical processes and effective recruitment of the necessary components. The cellular PAR level is tightly controlled by a network of regulatory proteins: PAR code writers, readers, and erasers. Impaired PAR metabolism is associated with the development of pathological processes causing oncological, cardiovascular, and neurodegenerative diseases. Pharmacological correction of the PAR level may represent a new approach to the treatment of various diseases.

Zinc-dependent Nucleosome Reorganization by PARP2

“…To support spFRET measurements (and, in part, EMSA), the nucleosomes were labeled with a donor-acceptor pair of Cy3 and Cy5 fluorophores (Figure 1a) attached to the neighboring gyres of nucleosomal DNA at the following positions: 13 and 91 bp (N p nucleosomes), 35 and 112 bp (N m nucleosomes) or 57 and 135 bp (N d nucleosomes) from the boundary of the 603 nucleosome positioning DNA sequence (23, 26). The labels placed at these positions allow efficient FRET and probing structural changes near and far from the boundary of the nucleosomal DNA (23, 26, 27). Single nucleosomes or their complexes with PARP2 freely diffusing in a solution were subjected to spFRET measurements and the data were presented as graphs describing the frequency distributions of nucleosomes by proximity ratio E PR (Figure 1b, d).…”

Overexpression of the WWE domain of RNF146 modulates poly-(ADP)-ribose dynamics at sites of DNA damage

“…PAR chains following laser micro-irradiation-induced DNA damage PAR chains show variable length and branching patterns [80], which can influence the number of PAR binding domains that can bind to each PAR chain. Recent findings indicate that linear PAR chains may extend to as much as 200 ADP-ribose units [21].…”

ADP-Ribosylation and Antiviral Resistance in Plants

“…MARylation processes are catalysed by mono(ADP-ribose) transferases (MARTs or PARP “monoenzymes”), whereas PARylation is catalysed by PARP “polyenzymes”, both of which use nicotinamide adenine dinucleotide (NAD+) as a donor of ADP-ribose for PAR (MAR) synthesis. This reaction also leads to the formation of nicotinamide as a collateral product ( Figure 1 ; [ 1 , 3 ]). The resultant ADPRylated proteins, including PARP itself and other protein targets, operate as regulators of various cellular signalling pathways.…”