02 May 2003 : Case report
PARP-1 protects the genome and suppresses tumor development: lessons from gene knock-out models
Z. WangMed Sci Monit 2003; 9(1): 76-0 :: ID: 15219
Abstract
Poly(ADP-ribose) polymerase (PARP-1), which catalyzes poly-ADP-ribosylation of nuclear proteins upon DNA damage, is a multifunctional molecule operative in a range of cellular processes including cell death, DNA repair and recombination, as well as in the maintenance of chromosome stability. Mice lacking PARP-1 are hypersensitive to g-radiation and exhibit telomere shortening, increased sister chromatid exchange and chromosomal aberrations, as well as chromosome gains and losses. Although low tumor incidence was observed in young animals, after multiple generations in a PARP-1 null background, mice were susceptible to malignancy. In addition, PARP-1 deficiency provoked epithelial tumor formation in mice heterozygous for p53 mutation. These tumors associated with dysfunctional telomeres and increased genomic instability, causing an LOH of p53. Interestingly, more than 45% of PARP-1–/– p53–/– mice developed brain tumors at a young age and the characteristics of these tumors are reminiscent of human medulloblastomas. We have also found that haploinsufficiency of Ku80, the DNA binding subunit of DNA-dependent protein kinase (DNA-PK), promotes HCC development in PARP-1 null mice. Molecular and cytogenetic analyses of these tumors will be discussed. Taken together, these data indicate that PARP-1 plays an important role in suppressing chromosome aberrations and tumorigenesis.
Keywords: PARP-1, p53, Ku80, genomic instability, medulloblastomas, hepatocellular carcinoma
Editorial
01 March 2024 : Editorial
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-ThalassemiaDOI: 10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
In Press
18 Mar 2024 : Clinical Research
Sexual Dysfunction in Women After Tibial Fracture: A Retrospective Comparative StudyMed Sci Monit In Press; DOI: 10.12659/MSM.944136
21 Feb 2024 : Clinical Research
Potential Value of HSP90α in Prognosis of Triple-Negative Breast CancerMed Sci Monit In Press; DOI: 10.12659/MSM.943049
22 Feb 2024 : Review article
Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...Med Sci Monit In Press; DOI: 10.12659/MSM.943168
23 Feb 2024 : Clinical Research
A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...Med Sci Monit In Press; DOI: 10.12659/MSM.943732
Most Viewed Current Articles
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
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
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