Poly(ADP-Ribose) Polymerases 1 and 2: Classical Functions and Interaction with New Histone Poly(ADP-Ribosyl)ation Factor HPF1

Poly(ADP-ribose) (PAR) is a negatively charged polymer, linear or branched, that consists of ADP-ribose monomers. PAR is synthesized by poly(ADP-ribose)polymerase (PARP) enzymes, which are activated upon DNA damage and use nicotinamide adenine dinucleotide (NAD(+)) as a substrate. The best-studied members of the PARP family, PARP1 and PARP2, are the most important nuclear proteins involved in many cell processes, including the regulation of DNA repair. PARP1 and PARP2 catalyze PAR synthesis and transfer to amino acid residues of target proteins, including autoPARylation. PARP1 and PARP2 are promising targets for chemotherapy in view of their key role in regulating DNA repair. A novel histone PARylation factor (HPF1) was recently discovered to modulate PARP1/2 activity by forming a transient joint active site with PARP1/2. Histones are modified at serine residues in the presence of HPF1. The general mechanism of the interaction between HPF1 and PARP1/2 is a subject of intense research now. The review considers the discovery and classical mechanism of PARylation in higher eukaryotes and the role of HPF1 in the process.

Automated summary

Poly(ADP-ribose) (PAR) is a negatively charged polymer composed of ADP-ribose monomers that is synthesized by poly(ADP-ribose)polymerase (PARP) enzymes upon DNA damage. PARP1 and PARP2 are the most well-studied members of the PARP family and play crucial roles in regulating DNA repair. A newly discovered histone PARylation factor (HPF1) modulates the activity of PARP1/2 by forming a transient joint active site with them. The review discusses the discovery and classical mechanism of PARylation in higher eukaryotes, as well as the role of HPF1 in this process.