[Molecular mechanisms of regulaion of transcription by PARP1]

Poly-ADP-ribosylation is a covalent post-translational modification of nuclear proteins that plays a key role in the immediate response of cells to genotoxic stress. Poly(ADP-ribose) polymerase (PARP) synthesizes long and branched polymers of ADP-ribose onto acceptor regulator proteins, and thereby change their activity. Metabolism of poly-ADP regulates DNA repair, cell cycle, replication, aging and death of cells, as well as remodeling of chromatin structure and gene transcription. PARP1 is one of the most common nuclear proteins; it is responsible for production of -90% of the polymers of ADP-ribose in the cell. PARP1 inhibitors are promising antitumor agents. At the same time, the current inhibitors target the catalytic domain of PARP1 that leads to.a number of side effects. Therefore, considering the potential benefits of PARP1 inhibitors for the treatment of multiple diseases, it is necessary to develop new strategies of PARP1 inhibition. PARP1 has a modular structure and has catalytic, transcription and DNA-binding activities. The review focuses primarily on the role of PARP1 in transcriptional regulation; the structure and functional organization of PARP1, as well as multiple ways of regulation of chromatin remodeling, DNA methylation and transcription are covered in detail. Studies of the molecular mechanisms of regulation of transcription factor PARP1 can serve as a basis for search and design of new inhibitors.