Poly(ADP-ribose)polymerases 1 and 2: Classical Functions and Interaction with HPF1 ‒ New Histone Poly(ADP-ribosyl)ation Factor

Abstract

Poly(ADP-ribose) (PAR) is a negatively charged polymer, linear and branched, consisting of ADP-ribose monomers. This polymer is synthesized by poly(ADP-ribose)polymerase (PARP) enzymes which are activated on DNA damage and use nicotinamide adenine dinucleotide (NAD+) as a substrate. The most studied members of the PARP family, PARP1 and PARP2, are the most important nuclear proteins involved in many cellular processes, including the regulation of DNA repair. PARP1 and PARP2 catalyze both the synthesis and transfer of poly(ADP-ribose) to amino acid residues of target proteins, including autoPARylation. In view of the key role in the regulation of the DNA repair process, PARP1 and PARP2 are promising targets for chemotherapy. Recently, a novel histone PARylation factor (HPF1) has been discovered to modulate PARP1/2 activity by forming a transient joint active site with PARP1/2. In the presence of HPF1, histone modification occurs at serine residues. The general mechanism of interaction between HPF1 and PARP1/2 is only beginning to be elucidated. In this review, we consider the discovery and classical mechanism of this important process in higher eukaryotes, as well as the role of a new histone PARylation factor in this HPF1 process.