Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

02 May 2003

Genetic cooperation between the Werner syndrome protein and poly(ADP-ribose) polymerase-1 in preventing complex chromosomal rearrangements and cancer in mice

M. Lebel

Med Sci Monit 2003; 9(1): 34- :: ID: 15097


Werner syndrome (WS) is a rare autosomal recessive disorder characterized by the premature onset of a number of age-related diseases, including cancers. The gene responsible for WS (WRN in human or Wrn in mouse) encodes a DNA helicase/exonuclease protein. Participation in a replication complex is among the several functions postulated for the Wrn protein [reviewed in 1]. The poly(ADP-ribose) polymerase-1 (PARP-1) enzyme, which is known to bind to DNA damage, is also associated with the DNA replication complex [2]. To determine if Wrn and PARP-1 enzymes act in concert during cell growth, mice with a mutation in the helicase domain of the Wrn gene (WrnDhel/Dhel mice) were crossed to PARP-1 null mice. Phenotypically, double mutant mice (PARP-1 null/WrnDhel/Dhel) developed tumors more rapidly than Wrn mutants. At the cellular levels, mouse embryonic fibroblasts derived from such PARP-1 null/WrnDhel/Dhel mice stop dividing abruptly unlike WrnDhel/Dhel or PARP-1 null cells. At the chromosomal level, PARP-1 null/WrnDhel/Dhel fibroblasts were distinguished by an increased frequency of chromatid breaks, chromosome rearrangements, and fragmentation. Interestingly, different sets of genes are rearranged in PARP-1 null/WrnDhel/Dhel cells compared to PARP-1 null or WrnDhel/Dhel cells. Finally, experiments have indicated that PARP-1 co-immunoprecipitate with the human WRN protein. These results suggest that WRN (or Wrn in mouse) and PARP-1 enzymes may be part of a complex involved in the processing of DNA breaks. References: 1.Lebel M: Werner syndrome: genetic and molecular basis of a premature aging disorder. Cell Mol Life Sci, 2001; 58: 857-867 2.Simbulan-Rosenthal CM, Rosenthal DS, Hilz H et al: The expression of poly(ADP-ribose) polymerase during differentiation-linked DNA replication reveals that it is a component of the multiprotein DNA replication complex. Biochemistry, 1996; 35: 11622-11633

Keywords: Werner’s syndrome, PARP-1, genomic instability, senescence, tumor progression



01 May 2022 : Editorial  

Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937048

Med Sci Monit 2022; 28:e937048


24 May 2022 : Clinical Research  

Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...

Med Sci Monit In Press; DOI: 10.12659/MSM.936962  

04 May 2022 : Clinical Research  

Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...

Med Sci Monit In Press; DOI: 10.12659/MSM.936069  

27 May 2022 : Clinical Research  

Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)

Med Sci Monit 2022; 28:e936547

In Press

25 May 2022 : Review article  

Narrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of Dislocation

Med Sci Monit In Press; DOI: 10.12659/MSM.935665  

24 May 2022 : Clinical Research  

Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...

Med Sci Monit In Press; DOI: 10.12659/MSM.936580  

24 May 2022 : Clinical Research  

Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...

Med Sci Monit In Press; DOI: 10.12659/MSM.936962  

23 May 2022 : Clinical Research  

Fully Automatic Knee Joint Segmentation and Quantitative Analysis for Osteoarthritis from Magnetic Resonanc...

Med Sci Monit In Press; DOI: 10.12659/MSM.936733  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

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

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750