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 MurciaMed Sci Monit 2003; 9(1): 42-0 :: ID: 15105
Abstract
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
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
12 Mar 2024 : Clinical Research
Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Pa...Med Sci Monit In Press; DOI: 10.12659/MSM.943126
12 Mar 2024 : Clinical Research
Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury Afte...Med Sci Monit In Press; DOI: 10.12659/MSM.943500
12 Mar 2024 : Review article
Optimizing Behçet Uveitis Management: A Review of Personalized Immunosuppressive StrategiesMed Sci Monit In Press; DOI: 10.12659/MSM.943240
12 Mar 2024 : Clinical Research
Metabolomic Alterations in Methotrexate Treatment of Moderate-to-Severe PsoriasisMed Sci Monit In Press; DOI: 10.12659/MSM.943360
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