Biological activity of poly(ADP-ribose)polymerase-1

摘要

Poly(ADP-ribose)polymerase-1 (PARP-1) catalyzes the polymerization of ADP-ribose units from NAD⁺ modules on target proteins, resulting in the attachment of linear or branched polymers. PARP-1 and its product poly(ADP-ribose) – PAR have recently received considerable attention because of their involvement in a wide range of cellular processes including chromatin modification, metabolism of nucleic acids, transcription regulation, and cell death. This review summarizes recent work on modular structure of six functional domains (A–F) of PARP-1 molecule in the context of three classic domains, i.e., DNA binding (DBD), automodification (AD) and catalytic (CD) released by proteolytic enzymes. A special attention is paid to subcellular localization and molecular mechanisms of PARP-1 posttranslational modifications, such as: poly(ADP-ribosylation), phosphorylation, acetylation and sumolyation. In addition, main functions of PARP-1 are discussed, focusing on the activity of this enzyme in DNA damage detection and repair, genome stability, and cell death.