Poly(ADP-ribose) polymerase-2: emerging transcriptional roles of a DNA-repair protein

• Published in: Cellular and molecular life sciences : CMLS 2012-12, Vol.69 (24), p.4079-4092
• Main Authors: Szántó, Magdolna, Brunyánszki, Attila, Kiss, Borbála, Nagy, Lilla, Gergely, Pál, Virág, László, Bai, Péter
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; Animals; Beta cells; Biochemistry; biogenesis; Biomedical and Life Sciences; Biomedicine; carcinogenesis; Cell Biology; centromeres; Chromatin Assembly and Disassembly; Deoxyribonucleic acid; DNA; DNA polymerase; DNA Repair; Enzymes; gene expression; Gene Expression Regulation; genome; Genomic Instability; Humans; inflammation; insulin resistance; Life Sciences; Metabolism; Mice; Mitochondria; Models, Genetic; NAD ADP-ribosyltransferase; Oxidative stress; Oxidative Stress - genetics; phenotype; Poly(ADP-ribose) Polymerases - chemistry; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - physiology; Protein Structure, Tertiary; Proteins; Review; Sirtuin 1 - metabolism; Sirtuin 1 - physiology; Spermatogenesis - genetics; spermiogenesis; telomeres; transcription (genetics); Transcription, Genetic
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-012-1003-8

Poly(ADP-ribose) polymerase (PARP)-2 is a nuclear enzyme that belongs to the PARP family and PARP-2 is responsible for 5–15 % of total cellular PARP activity. PARP-2 was originally described in connection to DNA repair and in physiological and pathophysiological processes associated with genome maintenance (e.g., centromere and telomere protection, spermiogenesis, thymopoiesis, azoospermia, and tumorigenesis). Recent reports have identified important rearrangements in gene expression upon the knockout of PARP-2. Such rearrangements heavily impact inflammation and metabolism. Metabolic effects are mediated through modifying PPARγ and SIRT1 function. Altered gene expression gives rise to a complex phenotype characterized primarily by enhanced mitochondrial activity that results both in beneficial (loss of fat, enhanced insulin sensitivity) and in disadvantageous (pancreatic beta cell hypofunction upon high fat feeding) consequences. Enhanced mitochondrial biogenesis provides protection in oxidative stress-related diseases. Hereby, we review the recent developments in PARP-2 research with special attention to the involvement of PARP-2 in transcriptional and metabolic regulation.