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

Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse

J. Menissier de Murcia, M. Ricoul, A. Huber, C. Niedergang, V. Schreiber, L. Sabatier, G. de Murcia

Med Sci Monit 2003; 9(1): 42- :: ID: 15105


PARP-1 and PARP-2 are until now the sole members of the PARP family whose catalytic activity is stimulated by DNA strand-breaks suggesting that they are both involved in the cellular response to DNA damage [1]. Like PARP-1–/– mice, PARP-2–/– mice are also sensitive to ionizing radiation and display genomic instability [2]. The deficiency in either PARP-1 [3–5] or PARP-2 [6] slows down the BER process. PARP-1–/–, PARP-2–/– double mutants are not viable and die around E7.5, a developmental stage when embryonic cells are hypersensitive to DNA-damage [7]. The demise during this developmental window is known to occur in embryos lacking BER factors (XRCC1 or APE), factors involved in double strand breaks repair (rad 50, rad 51) and Atr. Thus, PARP-1 and PARP-2 have complementary functions that are essential for development. Specific female embryonic lethality was observed in PARP-1+/–, PARP-2–/– mutant embryos at E9.5. Metaphase analyses at E8.5 highlight a specific instability of X-chromosomes in those females but not in males. X-chromosome missegregation and aneuploidy are the most frequent events suggesting a kinetochore defect that may lead to a mitotic catastrophe and developmental arrest around E9.5. Similar female-specific lethality was reported associated with mutations in DNA repair genes [8,9]. In these cases, even if a critical level of DNA repair capacity is reached, avoiding a complete early lethality, the poor DNA repair efficiency may lead to a severe genomic instability, detrimental first for the females. References: 1.Amé et al: J Biol Chem, 1999; 274: 17860-17868 2.Ménissier-de Murcia J et al: submitted 3.Beneke et al: Mol Cel Biol, 2000; 20: 6695-6703 4.Dantzer et al: Biochemistry, 2000; 39: 7559-7569 5.Masutani et al: Mutat Res, 2000; 406: 156-166 6.Schreiber et al: J Biol Chem, 2002; 277: 23028-23036 7.Heyer et al: Genes Dev, 2000; 14: 2072-2084 8.Cranston et al: Nat Genet, 1997; 17: 114-118 9.Healey et al: Nat Genet, 2000; 26: 362-364

Keywords: KO mice, NAD metabolism, BER, X-chromosome, genomic instability



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