Regulation of chromatin structure and chromatin-dependent transcription by poly(ADP-ribose) polymerase-1: possible targets for drug-based therapies.
Poly(ADP-ribose) Polymerase-1 (PARP-1) is the prototypical and most abundantly expressed member of a family of PARPs that catalyze the polymerization of ADP-ribose (ADPR) units from donor NAD' molecules on target proteins. PARP-1 plays roles in a variety of genomic processes, including the regulation of chromatin structure and transcription in response to specific cellular signals. PARP-1 also plays important roles in many stress-induced disease states. In this chapter, we review the molecular and cellular aspects of PARP-1's chromatin-modulating activities, as well as the impact that these chromatin-modulating activities have on the regulation of gene expression. In addition, we highlight the potential therapeutic use of drugs that target PARP-1's enzymatic activity for the treatment of human diseases
Wacker
David A
DA
Department of Molecular Biology and Genetics, Cornell University, 465 Biotechnology Building, Ithaca, NY 14853, USA.
Frizzell
Kristine M
KM
Zhang
Tong
T
Kraus
W Lee
WL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002875:Chromosomes / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009690:Nucleic Acid Conformation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011487:Protein Conformation; D014158:Transcription, Genetic
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D002843:Chromatin; D006657:Histones; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases