02 May 2003 : Original article
Functional study of poly(ADP-ribose) glycohydrolase (PARG)
U. Cortes, W. Tong, Z. Herceg, V. Petrilli, E. Jacobson, M. Jacobson, Z. WangMed Sci Monit 2003; 9(1): 14-0 :: ID: 15061
Abstract
Poly(ADP-ribosyl)ation of proteins is one of the earliest responses to DNA damage in most eukaryotic cells. This posttranslational modification of nuclear proteins is achieved by the enzyme poly(ADP-ribose) polymerase (PARP-1), which synthesizes branched polymers of ADP-ribose (pADPr). Poly(ADP-ribose) polymers are then rapidly catabolized by the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG). Although inhibition or depletion of PARP-1 demonstrates that PARP-1 and poly(ADP-ribosyl)ation play a role in cell proliferation and death, stress response, cell toxicity, DNA repair, recombination, and chromosomal stability, the exact functions of poly(ADP-ribosyl)ation and PARP-1 are largely unknown. This may be due to insufficient knowledge about PARG function, since only a few studies regarding pADPr catabolism have been performed. To better define the functions of PARG and poly(ADP-ribosyl)ation in vivo, we disrupted the PARG gene in ES cells by homologous recombination. Intercrossing of PARG heterozygous (PARG+/D) mice produced a normal mendelian ratio of PARG+/+, PARG+/D and PARGD/D offspring. Interestingly, homozygous PARG knockout mice developed normally, and were healthy and fertile. Expression analysis demonstrated the absence of PARG mRNA in PARGD/D cells and mice, and in the PARG+/D cells, PARG expression was at half of that of wild-type counterparts. These data indicate that PARG is not essential for normal development. Detailed analysis of pADPr metabolism in PARGD/D cells and inflammation response of PARGD/D mice indicate that PARG activity is important for controlling PARP-1 activity in vivo, possibly by regulating its auto-modifications.
Keywords: PARG, Poly(ADP-ribosyl)ation, Gene Targeting
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
08 Mar 2024 : Laboratory Research
Evaluation of Retentive Strength of 50 Endodontically-Treated Single-Rooted Mandibular Second Premolars Res...Med Sci Monit In Press; DOI: 10.12659/MSM.944110
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952